Strain Assessment in Aortic Stenosis: Pathophysiology and Clinical Utility.

Contemporary echocardiographic criteria for grading aortic stenosis severity have remained relatively unchanged, despite significant advances in noninvasive imaging techniques over the last 2 decades. More recently, attention has shifted to the ventricular response to aortic stenosis and how this might be quantified. Global longitudinal strain, semiautomatically calculated from standard two-dimensional echocardiographic images, has been the focus of extensive research. Global longitudinal strain is a sensitive marker of subtle hypertrophy-related impairment in left ventricular function and has shown promise as a relatively robust prognostic marker, both independently and when added to severity classification systems. Herein we review the pathophysiological basis underpinning the potential utility of global longitudinal strain in the assessment of aortic stenosis, as well as its potential role in quantifying myocardial recovery and prognostic discrimination following aortic valve replacement.

Machine learning prediction of progressive subclinical myocardial dysfunction in moderate aortic stenosis.

Background: Moderate severity aortic stenosis (AS) is poorly understood, is associated with subclinical myocardial dysfunction, and can lead to adverse outcome rates that are comparable to severe AS. Factors associated with progressive myocardial dysfunction in moderate AS are not well described. Artificial neural networks (ANNs) can identify patterns, inform clinical risk, and identify features of importance in clinical datasets. Methods: We conducted ANN analyses on longitudinal echocardiographic data collected from 66 individuals with moderate AS who underwent serial echocardiography at our institution. Image phenotyping involved left ventricular global longitudinal strain (GLS) and valve stenosis severity (including energetics) analysis. ANNs were constructed using two multilayer perceptron models. The first model was developed to predict change in GLS from baseline echocardiography alone and the second to predict change in GLS using data from baseline and serial echocardiography. ANNs used a single hidden layer architecture and a 70%:30% training/testing split. Results: Over a median follow-up interval of 1.3 years, change in GLS (≤ or >median change) could be predicted with accuracy rates of 95% in training and 93% in testing using ANN with inputs from baseline echocardiogram data alone (AUC: 0.997). The four most important predictive baseline features (reported as normalized % importance relative to most important feature) were peak gradient (100%), energy loss (93%), GLS (80%), and DI < 0.25 (50%). When a further model was run including inputs from both baseline and serial echocardiography (AUC 0.844), the top four features of importance were change in dimensionless index between index and follow-up studies (100%), baseline peak gradient (79%), baseline energy loss (72%), and baseline GLS (63%). Conclusions: Artificial neural networks can predict progressive subclinical myocardial dysfunction with high accuracy in moderate AS and identify features of importance. Key features associated with classifying progression in subclinical myocardial dysfunction included peak gradient, dimensionless index, GLS, and hydraulic load (energy loss), suggesting that these features should be closely evaluated and monitored in AS.

Coronary angiography of the ex-situ beating donor heart in a portable organ care system.

OBJECTIVES: To determine safety and feasibility of ex-situ coronary angiography. BACKGROUND: To cater for the perpetually growing demand for heart donors, interest in donation following circulatory death (DCD) has been rekindled. Further pursuit of donor pool expansion has led to eligibility extension to "marginal" donors who are at higher risk of coronary artery disease (CAD). Excluding CAD in potentially eligible DCD donors, for whom ante-mortem angiography is commonly not permitted, is therefore challenging. Ex-situ coronary angiography serves as an ethical and feasible diagnostic tool to assess for preclusive CAD. METHODS: We undertook a systematic review of the published literature and institutional retrospective review of case experience with ex-situ coronary angiography of donor hearts, supported by a portable organ care system. RESULTS: Combined literature and institutional case review yielded nine total cases of ex-situ coronary angiography of donor human hearts plus one experimental porcine model. Of the eight cases of ex-situ coronary angiography performed at our institute, all were conducted without complication or injury to the allograft. Two thirds of reported human cases have proceeded to successful transplantation. CONCLUSIONS: Diagnostic coronary angiography of the ex-situ beating donor heart is safe, feasible, and demonstrates novel clinical utility in mitigating subsequent transplantation of unsuitable allografts. In the setting of suspected coronary atherosclerosis of the donor heart, which may preclude favorable transplantation outcomes, ex-situ coronary angiography should be considered at eligible transplant centers.

Extracorporeal Membrane Oxygenation-Supported Transcatheter Mitral Valve-in-Valve Replacement and Paravalvular Plugging for Critical Prosthetic Mitral Stenosis.

We present the case of a patient with rapidly progressive bioprosthetic mitral valve stenosis in the setting of end-stage renal failure. Critical valve stenosis led to cardiogenic shock requiring full hemodynamic support. Emergent extracorporeal membrane oxygenation-supported transcatheter mitral valve-in-valve implantation was successfully undertaken as a life-saving measure with an excellent final result. (Level of Difficulty: Advanced.).

Heart Failure Therapies for the Prevention of HER2-Monoclonal Antibody-Mediated Cardiotoxicity: A Systematic Review and Meta-Analysis of Randomized Trials.

Monoclonal antibodies including trastuzumab, pertuzumab, and antibody-drug conjugates, form the backbone of HER2-positive breast cancer therapy. Unfortunately, an important adverse effect of these agents is cardiotoxicity, occurring in approximately 10% of patients. There is increasing published data regarding prevention strategies for cardiotoxicity, though seldom used in clinical practice. We performed a systematic review and meta-analysis of randomized-controlled trials to evaluate pharmacotherapy for the prevention of monoclonal HER2-directed antibody-induced cardiotoxicity in patients with breast cancer. Online databases were queried from their inception until October 2021. Effects were determined by calculating risk ratios (RRs) and 95% confidence intervals (CI) or mean differences (MD) using random-effects models. We identified five eligible trials. In the three trials (n = 952) reporting data on the primary outcome of cardiotoxicity, there was no clear effect for patients assigned active treatment compared to control (RR = 0.90, 95% CI 0.63 to 1.29, p = 0.57). Effects were similar for ACE-I/ARB and beta-blockers (p homogeneity = 0.50). Active treatment reduced the risk of HER2 therapy interruptions (RR = 0.57, 95% CI 0.43 to 0.77, p < 0.001) with similar findings for ACE-I/ARB and beta-blockers (p homogeneity = 0.97). Prophylactic treatment with ACE-I/ARB or beta-blocker therapy may be of value for cardio-protection in patients with breast cancer prescribed monoclonal antibodies. Further, adequately powered randomized trials are required to define the role of routine prophylactic treatment in this patient group.

Twice Bitten, Thrice Shy: A Case of Recurrent Isolated Cardiac Sarcoidosis in the Transplanted Heart.

We present a case of recurrent isolated cardiac sarcoidosis, 3 years post-heart transplantation. The case highlights the scarcity of data on the utility of immunosuppression in cardiac sarcoidosis and, in particular, raises questions about the optimal immunosuppression regimen in transplant recipients. (Level of Difficulty: Advanced.).

The use of direct oral anticoagulants in patients with ventricular assist devices: Is there hope for Factor Xa inhibition?

The use of continuous-flow ventricular assist devices (cf-VAD) necessitates systemic anticoagulation, routinely with vitamin K antagonists (VKA). Newer direct oral anticoagulants (DOACs) have significant advantages over VKA in providing a predictable level of systemic anticoagulation without frequent monitoring or strict dietary surveillance. Despite randomized evidence demonstrating their usefulness in several conditions including atrial fibrillation, there is limited data pertaining to their use in cf-VAD patients. Early reports of adverse outcomes has resulted in a Class III recommendation, advising against DOACs generally in cf-VAD patients. Recent reports suggest there may be a role for certain DOACs; as such we present a systematic review identifying studies reporting DOAC uses in patients with a cf-VAD. We identified eight pertinent studies, including a single randomized controlled trial and seven case reports/series. Limited numbers and significant study heterogeneity limits interpretation; however, Factor Xa inhibitors appear to be feasible alternatives, favorable to direct thrombin inhibitors, although further research is required.

Colonic malakoplakia in a dual stem cell and cardiac transplant recipient: A case report and literature review.

We describe the first published case of malakoplakia in a dual stem cell and cardiac transplant recipient. In the 2 months following cardiac transplantation, our patient developed persistent diarrhea and recurrent E coli bacteremia. Biopsies obtained from areas of colonic thickening revealed malakoplakia. Despite improvement in symptoms with prolonged antimicrobial therapy and reduction of his immunosuppression, he eventually died from sepsis. Our case highlights not only the importance of the timely diagnosis of this rare disorder, but also the difficulty in determining optimal treatment duration, particularly where excision of involved areas is not possible, as data on this disease are lacking. Here we describe our case and review the available literature published on malakoplakia in the cardiac transplant population.

Recanalization of an atretic left internal mammary graft after bypass surgery for an anomalous left main coronary artery origin: a case report.

BACKGROUND: The inter-arterial anomalous course of the left main coronary artery (LMCA) originating from the right coronary sinus of Valsalva is a rare, though potentially lethal pathology. Coronary artery bypass grafting is a potential surgical therapy with previously reported success, however, there is concern for the possibility of graft occlusion in the setting of competitive native vessel flow. CASE SUMMARY: A 48-year-old gentleman presented to our facility with a non-ST elevation acute coronary syndrome. A malignant anomalous course of the LMCA was confirmed using invasive coronary angiography and computed tomography (CT). The patient underwent surgical revascularization of the left anterior descending artery with a left internal mammary artery (LIMA) graft, which was found to be atretic on follow-up CT. Seven years later the patient underwent repeat CT imaging, which confirmed recanalization of the previously atretic LIMA. DISCUSSION: We present the first documented case of a patient with spontaneous recanalization of an occluded LIMA following bypass surgery for an inter-arterial anomalous course of the LMCA. We postulate that the dynamic obstruction of the anomalous LMCA led to variable flow dependence on the bypass graft and subsequent atresia of the LIMA, due to the favourable native flow conditions in the absence of significant obstructive coronary disease. The exact mechanism of LIMA recanalization remains unclear, but in our case may have been partly mediated by a small increase in left main plaque.

Pushing beyond the limit: a novel clinical sign of thoracic aortic dissection.

The timely diagnosis of aortic dissection is notoriously confounded by unreliable symptomatology. We present a previously unreported clinical sign: thoracic pain reproduced by abdominal palpation. Our case illustrates the dependence of traditional clinical features on the anatomical location of an aortic dissection and lends weight to the concept of aortic pain as being a dynamic product of inter-related changes in intraluminal pressure, volume, wall stress and diameter. The clinical sign we describe may be very specific of acute aortic pathology.