Machine Learning Quantification of Pulmonary Regurgitation Fraction from Echocardiography.

Assessment of pulmonary regurgitation (PR) guides treatment for patients with congenital heart disease. Quantitative assessment of PR fraction (PRF) by echocardiography is limited. Cardiac MRI (cMRI) is the reference-standard for PRF quantification. We created an algorithm to predict cMRI-quantified PRF from echocardiography using machine learning (ML). We retrospectively performed echocardiographic measurements paired to cMRI within 3 months in patients with ≥ mild PR from 2009 to 2022. Model inputs were vena contracta ratio, PR index, PR pressure half-time, main and branch pulmonary artery diastolic flow reversal (BPAFR), and transannular patch repair. A gradient boosted trees ML algorithm was trained using k-fold cross-validation to predict cMRI PRF by phase contrast imaging as a continuous number and at > mild (PRF ≥ 20%) and severe (PRF ≥ 40%) thresholds. Regression performance was evaluated with mean absolute error (MAE), and at clinical thresholds with area-under-the-receiver-operating-characteristic curve (AUROC). Prediction accuracy was compared to historical clinician accuracy. We externally validated prior reported studies for comparison. We included 243 subjects (median age 21 years, 58% repaired tetralogy of Fallot). The regression MAE = 7.0%. For prediction of > mild PR, AUROC = 0.96, but BPAFR alone outperformed the ML model (sensitivity 94%, specificity 97%). The ML model detection of severe PR had AUROC = 0.86, but in the subgroup with BPAFR, performance dropped (AUROC = 0.73). Accuracy between clinicians and the ML model was similar (70% vs. 69%). There was decrement in performance of prior reported algorithms on external validation in our dataset. A novel ML model for echocardiographic quantification of PRF outperforms prior studies and has comparable overall accuracy to clinicians. BPAFR is an excellent marker for > mild PRF, and has moderate capacity to detect severe PR, but more work is required to distinguish moderate from severe PR. Poor external validation of prior works highlights reproducibility challenges.

Longitudinal Changes in Exercise Capacity in Patients Who Underwent Ross Procedure and Mechanical Aortic Valve Replacement: Does the Type of Surgery Matter?

The surgical options for significant aortic valve disease include either Ross procedure (RP) or aortic valve replacement (AVR). The exercise stress test is routinely performed in these patients to assess the objective functional capacity. This retrospective study was conducted to evaluate the differences and the longitudinal changes of exercise capacity in patients following the RP and AVR for aortic valve disease. This is an IRB approved retrospective study and included patients who had either RP or AVR performed for aortic valve disease and had at least one exercise stress test performed after the surgical procedure. Patients with other congenital heart disease, pacemaker or defibrillators, and those with inadequate data were excluded. Demographic data including age at surgery, type of surgery and type of aortic valve was collected. Data regarding treadmill cardiopulmonary exercise test (CPET) was also collected. A total of 47 patients met inclusion criteria and were equally represented in each group, i.e. RP [n = 23, 73.9% male, age at surgery 11.2 (4.5-15.9) years] vs. AVR [n = 24, 88% mechanical AVR, 60.9% male, age at surgery 15.1 (12.8-19.4) years]. There was a significant decline in predicted oxygen consumption (%VO2) at time of first post-operative CPET in patients after AVR compared to RP (79 vs. 88%, p = 0.048) over a similar accrued median interval follow-up (4.6 vs. 6.2 years, p = 0.2). The longitudinal follow-up analysis of following AVR (n = 11, 54.5% male, median inter-test duration of 5 years) showed significant decline in peak exercise capacity or VO2 (34.2 vs. 26.2 vs., p = 0.006). In contrast, after RP (n = 12 patients [58.3% male, median inter-test duration 7.1 of years], exercise capacity and other key parameters remained preserved. In this small sentinel study, we report a better initial exercise capacity among patients after RP compared to AVR over an intermediate follow-up. During longitudinal follow-up in a subset of patients, exercise capacity remained preserved amongst the RP group while it further declined in the AVR group.

Coronary artery embolism in a patient with Fontan palliation: a rare complication.

Coronary artery embolism is extremely rare in children with Fontan palliation. We report a 10-year-old boy with hypoplastic left heart syndrome post-Fontan procedure who presented with acute onset chest pain and ST-segment changes on electrocardiogram. Cardiac catheterisation revealed coronary artery emboli requiring stent placement. Our case highlights the importance of evaluating chest pain in a systematic manner in Fontan patients as acute coronary artery embolism can be a part of the spectrum of well-known thromboembolic complications.

Anchored p90 ribosomal S6 kinase 3 is required for cardiac myocyte hypertrophy.

RATIONALE: Cardiac myocyte hypertrophy is the main compensatory response to chronic stress on the heart. p90 ribosomal S6 kinase (RSK) family members are effectors for extracellular signal-regulated kinases that induce myocyte growth. Although increased RSK activity has been observed in stressed myocytes, the functions of individual RSK family members have remained poorly defined, despite being potential therapeutic targets for cardiac disease. OBJECTIVE: To demonstrate that type 3 RSK (RSK3) is required for cardiac myocyte hypertrophy. METHODS AND RESULTS: RSK3 contains a unique N-terminal domain that is not conserved in other RSK family members. We show that this domain mediates the regulated binding of RSK3 to the muscle A-kinase anchoring protein scaffold, defining a novel kinase anchoring event. Disruption of both RSK3 expression using RNA interference and RSK3 anchoring using a competing muscle A-kinase anchoring protein peptide inhibited the hypertrophy of cultured myocytes. In vivo, RSK3 gene deletion in the mouse attenuated the concentric myocyte hypertrophy induced by pressure overload and catecholamine infusion. CONCLUSIONS: Taken together, these data demonstrate that anchored RSK3 transduces signals that modulate pathologic myocyte growth. Targeting of signaling complexes that contain select kinase isoforms should provide an approach for the specific inhibition of cardiac myocyte hypertrophy and for the development of novel strategies for the prevention and treatment of heart failure.

p90 ribosomal S6 kinase 3 contributes to cardiac insufficiency in α-tropomyosin Glu180Gly transgenic mice.

Myocardial interstitial fibrosis is an important contributor to the development of heart failure. Type 3 p90 ribosomal S6 kinase (RSK3) was recently shown to be required for concentric myocyte hypertrophy under in vivo pathological conditions. However, the role of RSK family members in myocardial fibrosis remains uninvestigated. Transgenic expression of α-tropomyosin containing a Glu180Gly mutation (TM180) in mice of a mixed C57BL/6:FVB/N background induces a cardiomyopathy characterized by a small left ventricle, interstitial fibrosis, and diminished systolic and diastolic function. Using this mouse model, we now show that RSK3 is required for the induction of interstitial fibrosis in vivo. TM180 transgenic mice were crossed to RSK3 constitutive knockout (RSK3(-/-)) mice. Although RSK3 knockout did not affect myocyte growth, the decreased cardiac function and mild pulmonary edema associated with the TM180 transgene were attenuated by RSK3 knockout. The improved cardiac function was consistent with reduced interstitial fibrosis in the TM180;RSK3(-/-) mice as shown by histology and gene expression analysis, including the decreased expression of collagens. The specific inhibition of RSK3 should be considered as a potential novel therapeutic strategy for improving cardiac function and the prevention of sudden cardiac death in diseases in which interstitial fibrosis contributes to the development of heart failure.

Transmyocardial migration of a temporary epicardial pacing wire: a pediatric case report.

Transmyocardial migration of a retained temporary epicardial pacing wire has been rarely reported in adult patients after heart surgery. We present the case of a child in whom a temporary epicardial pacing wire was discovered incidentally in the right ventricular outflow tract one year after surgical repair of congenital heart disease. The pacing wire was subsequently extracted using the snare method during cardiac catheterization. Clinicians caring for patients after congenital heart surgery should be aware of this uncommon though potentially life-threatening complication.

The scaffold protein muscle A-kinase anchoring protein ß orchestrates cardiac myocyte hypertrophic signaling required for the development of heart failure.

BACKGROUND: Cardiac myocyte hypertrophy is regulated by an extensive intracellular signal transduction network. In vitro evidence suggests that the scaffold protein muscle A-kinase anchoring protein ß (mAKAPß) serves as a nodal organizer of hypertrophic signaling. However, the relevance of mAKAPß signalosomes to pathological remodeling and heart failure in vivo remains unknown. METHODS AND RESULTS: Using conditional, cardiac myocyte-specific gene deletion, we now demonstrate that mAKAPß expression in mice is important for the cardiac hypertrophy induced by pressure overload and catecholamine toxicity. mAKAPß targeting prevented the development of heart failure associated with long-term transverse aortic constriction, conferring a survival benefit. In contrast to 29% of control mice (n=24), only 6% of mAKAPß knockout mice (n=31) died in the 16 weeks of pressure overload (P=0.02). Accordingly, mAKAPß knockout inhibited myocardial apoptosis and the development of interstitial fibrosis, left atrial hypertrophy, and pulmonary edema. This improvement in cardiac status correlated with the attenuated activation of signaling pathways coordinated by the mAKAPß scaffold, including the decreased phosphorylation of protein kinase D1 and histone deacetylase 4 that we reveal to participate in a new mAKAP signaling module. Furthermore, mAKAPß knockout inhibited pathological gene expression directed by myocyte-enhancer factor-2 and nuclear factor of activated T-cell transcription factors that associate with the scaffold. CONCLUSIONS: mAKAPß orchestrates signaling that regulates pathological cardiac remodeling in mice. Targeting of the underlying physical architecture of signaling networks, including mAKAPß signalosome formation, may constitute an effective therapeutic strategy for the prevention and treatment of pathological remodeling and heart failure.