Intranasal dexmedetomidine for transthoracic echocardiography in infants with shunt-dependent single ventricle heart disease.

OBJECTIVES: We investigated the efficacy and complication profile of intranasal dexmedetomidine for transthoracic echocardiography sedation in patients with single ventricle physiology and shunt-dependent pulmonary blood flow during the high-risk interstage period. METHODS: A single-centre, retrospective review identified interstage infants who received dexmedetomidine for echocardiography sedation. Baseline and procedural vitals were reported. Significant adverse events related to sedation were defined as an escalation in care or need for any additional/increased inotropic support to maintain pre-procedural haemodynamics. Minor adverse events were defined as changes from baseline haemodynamics that resolved without intervention. To assess whether sedation was adequate, echocardiogram reports were reviewed for completeness. RESULTS: From September to December 2020, five interstage patients (age 29-69 days) were sedated with 3 mcg/kg intranasal dexmedetomidine. The median sedation onset time and duration time was 24 minutes (range 12-43 minutes) and 60 minutes (range 33-60 minutes), respectively. Sedation was deemed adequate in all patients as complete echocardiograms were accomplished without a rescue dose. When compared to baseline, three (60%) patients had a >10% reduction in heart rate, one (20%) patient had a >10% reduction in oxygen saturations, and one (20%) patient had a >30% decrease in blood pressure. Amongst all patients, no significant complications occurred and haemodynamic changes from baseline did not result in need for intervention or interruption of study. CONCLUSIONS: Intranasal dexmedetomidine may be a reasonable option for echocardiography sedation in infants with shunt-dependent single ventricle heart disease, and further investigation is warranted to ensure efficacy and safety in an outpatient setting.

Genetic Testing in Pediatric Cardiomyopathy.

Genetic testing is recommended in patients with dilated cardiomyopathy (DCM); however, limited studies demonstrate high yields of genetic testing in non-hypertrophic (HCM) patients. Furthermore, there is sparse genotype-phenotype data in pediatric DCM patients. We performed a retrospective review of 70 consecutive probands with cardiomyopathy (non-HCM) who underwent genetic evaluation. Mean age at presentation was 5.48 years. Echocardiography revealed mean ejection fraction of 32.4%. The LVEDd z score ranged from - 5.7 to + 15.9. Cardiomyopathy was classified as dilated in 56, 10 with non-compaction, 2 with restrictive, and 2 with ARVC. TTN gene mutations were the most common gene involved. Genetic testing was negative in 16/70 (23%) giving a yield of 77% including VUS. 33% (23/70) of probands had a positive family history among whom the diagnostic yield was 57% (13/23) for pathogenic mutations. Yield for positive genetic testing in the DCM with positive family history group was 9/18 (50%). There were 6 deaths (9%) and 26/70 (37%) underwent transplantation. More frequent cardiac transplantations (48 vs. 34%) and deaths (17 vs. 2%) were seen in mutation-positive vs. mutation-negative subgroups. This study demonstrates an increasing yield of genetic testing in DCM although with a high rate of VUS detection. Use of genetic information for better management and prognostication will require big data analysis.

Clinical, Experimental, and Computational Validation of a New Doppler-Based Index for Coarctation Severity Assessment.

BACKGROUND: Long-term morbidity including hypertension often persists in coarctation patients despite current guidelines. Coarctation severity can be invasively assessed via peak-to-peak catheter pressure gradient (PPCG), which is estimated noninvasively via simplified Bernoulli equation and conventionally reported as peak instantaneous Doppler gradient (PIDG). However, underlying simplifications of the equation limit diagnostic accuracy. We studied the diagnostic performance of a new Doppler-based diastolic index called the continuous flow pressure gradient (CFPG) versus conventional indices in assessing coarctation severity. METHODS: In a rabbit model mimicking human aortic coarctation, temporal blood pressure waveforms revealed the diastolic instantaneous pressure gradients and spectral Doppler features impacted by coarctation severity. We therefore hypothesized that CFPG provides superior correlation with coarctation gradients measured invasively. PIDG and CFPG were quantified using color flow echocardiography in humans and rabbits with discrete coarctations. Results were compared with PPCG in rabbits (n = 34) and arm-leg systolic gradients (n = 25) in humans via 1-way analysis of variance, Pearson's correlation, linear regression, and Bland-Altman analysis. RESULTS: A threshold of CFPG ≥ 4.6 mm Hg was identified via the Youden index as representative of PPCG ≥ 20 mm Hg (the current guideline value for coarctation intervention) in rabbits, while a CFPG ≥1.0 mm Hg represented an arm-leg systolic gradient ≥20 mm Hg in humans. Accuracy measures revealed superior correlation of CFPG (R2 > 0.80) and mild receiver operating characteristic improvement (area under the receiver operating characteristic curve, 0.94-0.95) compared with PIDG (R2 < 0.63; area under the receiver operating characteristic curve, 0.89-0.95). Inter-/intraobserver variability tested by intraclass correlation coefficient revealed measurement reliability with differences ≤8.2% and 10.7%, respectively. Computational simulations of anesthetized versus conscious hemodynamics showed parameters were minimally impacted by isoflurane inherent in the data used to derive CFPG. These results confirm the potential diagnostic accuracy of CFPG in echocardiography-based coarctation severity assessment. We are optimistic that CFPG will be useful for translation of results from preclinical studies that revisit current guidelines to limit morbidity in humans with aortic coarctation.