Genetic mutations, pathology, and single-nucleus transcriptomic landscape in LVHT patients reveal differential progression to heart transplantation.

Trabeculation and left ventricular hypertrabeculation/noncompaction

Noncompaction cardiomyopathy, a frequently overlooked entity (…but beware of over diagnosis!)

Overdiagnosis of Left Ventricular Noncompaction

The 2016 International Society for Heart Lung Transplantation listing criteria for heart transplantation: A 10-year update

Objective Isolated non-compaction of the ventricular myocardium (INVM) is a rare disorder of endocardial morphogenesis characterized by numerous, excessively ventricular trabeculations and deep intertrabecular recesses. The aim of this study was to investigate the clinical features of INVM. Methods Ages of the 4 patients ranged from 6 to 14 years (average age was 9.5 years). Three were male and 1 was female. Electrocardiogram, chest X-ray and echocardiography were studied. One case was examined with myocardial radioisotope scanning and one case accepted cardiac catheterization, ventriculography and coronary arteriography. Results Paroxysmal chest pain, short breath and dizziness were the main symptoms. Cardiac dilatation and decreased intensity of heart sounds were found in all cases. Cardiac arrhythmia was found in two cases. grade Ⅱ systolic murmur was on apex area of heart. Four cases developed myocardium ischemia demonstrated on electrocardiogram. Premature ventricular contraction was found in 2 cases. One case had paroxysmal ventricular tachycardia and complete right bundle branch block. Cardiac dilatation and cardiothoracic ratio>0.6 were noticed in chest X-ray checkup. Echocardiographic examination showed that numerous prominent ventricular trabeculations and deep intertrabecular recesses were presented in ventricle. The depths of the intertrabecular recesses were assessed by a quantitative echocardiographic X-to-Y ratio, which gradually decreased from mitral valve level to apex. Color Doppler study discovered a typically forward and reversed flow between prominent trabeculations during the cardiac cycle. Cardiac systolic function was decreased in 2 cases and diastolic function was decreased in 1 case. Two patients had moderate mitral incompetence. Ventriculography showed disarrangement of trabeculation and radial filling defect. Conclusion INVM is a rare entity of unknown etiology. It is characterized by numerous prominent trabeculations in the ventricular wall. INVM is accompanied by three major cardiac risks: (1) depressed ventricular function; (2) ventricular arrhythmia and (3) endocardial clotting with systemic embolization. Distinct morphological features can be found with two-dimensional echocardiography. Echocardiogram is a promising first-line diagnostic tool for INVM. Key words: Heard defects, congenital; Ventricular dysfunction; Diagnosis; Echocardiography

A 21-year-old man was admitted to the hospital with exertional dyspnea. At the age of 14, he was diagnosed with Danon disease by genetic analysis (a 2–base-pair deletion at positions 288 and 289 in exon 3 was identified in the lysosome-associated membrane protein-2 [LAMP2] gene of the patient, which led to a frameshift and resulted in a premature stop codon). A chest radiograph demonstrated moderate cardiomegaly (cardiothoracic ratio of 58%). The ECG exhibited normal sinus rhythm, wide and bifid P waves with a duration of 170 ms, complete left bundle-branch block with a QRS duration of 200 ms, and a leftward axis (−2°; Figure 1). Figure 1. Twelve-lead ECGs. Echocardiography revealed left ventricular (LV) dilatation with an end-diastolic internal dimension of 60 mm and diffusely hypokinetic LV wall motion with fractional shortening of 8% (Figure 2; Movie I of the online-only Data Supplement). …

OCCULT NONCOMPACTION CARDIOMYOPATHY LEADING TO CARDIOGENIC SHOCK: AN INFREQUENT YET DEADLY DIAGNOSIS

Institution-level strategic changes may be associated with heart transplant volume and outcomes. To describe changes in practice that markedly increased heart transplant volume at a single center, as well as associated patient characteristics and outcomes. A pre-post cohort study was conducted of 107 patients who underwent heart transplant between September 1, 2014, and August 31, 2019, at Yale New Haven Hospital before (September 1, 2014, to August 31, 2018; prechange era) and after (September 1, 2018, to August 31, 2019; postchange era) a strategic change in patient selection by the heart transplant program. Strategic change in donor and recipient selection at Yale New Haven Hospital that occurred in August 2018. Outcome measures were transplant case volume, donor and recipient characteristics, and 180-day survival. A total of 49 patients (12.3 per year; 20 women [40.8%]; median age, 57 years [interquartile range {IQR}, 50-63 years]) received heart transplants in the 4 years of the prechange era and 58 patients (58 per year; 19 women [32.8%]; median age, 57 years [IQR, 52-64 years]) received heart transplants in the 1 year of the postchange era. Organ offers were more readily accepted in the postchange era, with an offer acceptance rate of 20.5% (58 of 283) compared with 6.4% (49 of 768) in the prechange era (P < .001). In the postchange era, donor hearts were accepted with a higher median number of prior refusals by other centers than in the prechange era (16.5 [IQR, 6-38] vs 3 [IQR, 1-6]; P < .001). Hearts accepted in the postchange era were from older donors than in the prechange era (median age, 40 years [IQR, 29-48 years] vs 30 years [IQR, 24-42 years]; P < .001). Recipients had a significantly shorter time on the waiting list in the postchange era compared with prechange era (median, 41 days [IQR, 12-289 days] vs 242 days [IQR, 135-428 days]; P < .001). More patients were supported on temporary circulatory assist devices preoperatively in the postchange era than the prechange era (14 [24.1%] vs 0; P < .001). Survival rates at 180 days were not significantly different (43 [87.8%] in the prechange era vs 52 [89.7%] in the postchange era). Mortality while on the waiting list was similar (2.8 deaths per year in the prechange era vs 3 deaths per year in the postchange era). During the comparable time period, 4 other regional centers had volume change ranging from -10% to 68%, while this center's volume increased by 374%. This study suggests that strategic changes in donor heart and recipient selection may significantly increase the number of heart transplants while maintaining short-term outcomes comparable with more conservative patient selection. Such an approach may augment the allocation of currently unused donor hearts.

Funding Acknowledgements Type of funding sources: None. Background Left atrial (LA) dysfunction is associated with poorer outcomes in many disease processes. Left atrial strain (LAS) is a novel two-dimensional (2D) quantitative analysis of LA function. Cardiac transplantation directly involves the LA during implantation of the donor heart. Traditional echocardiographic indices after transplantation have demonstrated value in correlating with acute cellular rejection (ACR), morbidity and mortality over short- and long-term follow-up. The prognostic value of LA strain has not been previously investigated in this cohort. Purpose We hypothesized that incrementally impaired LA strain in post cardiac transplant patients with varying degrees of ACR may be prognostic of poorer outcomes on long term follow-up. Methods 87 Heart transplant patients, assessed between 2009 and 2015, underwent transthoracic echocardiography and endomyocardial biopsy. 2D strain analysis on the LV and LA were performed along with traditional echocardiographic parameters. Patients were grouped according to peak LAS (PALS) tertiles and rejection burden history was assessed and grouped according to ACR burden at a median of 12 (±5.4) months post transplantation. The primary endpoint was all-cause mortality at follow-up. Results 12 patients met the primary endpoint over a median follow-up of 66 ± 51 months. The mean LA PALS was significantly different across the tertiles (lowest tertile 12.29 ± 2.5% vs middle tertile 17.89 ± 1.1% vs highest tertile 24.54 ± 4.2%; p &amp;lt;0.0001). LA strain dispersion was also significantly different between the tertiles (61.03 ± 25.8ms vs 41.8 ± 15.8ms vs 44.8 ± 18.8ms; p &amp;lt;0.001). All other clinical and echocardiographic parameters were non-significant between the tertiles however, there was a trend towards a lower PALS in the higher rejection burden group. Kaplan Meier curves demonstrated that survival over follow-up was significantly worse in the lower tertile LA PALS group compared to the highest tertiles LA PALS group (Log-rank test = p &amp;lt; 0.0001). The lowest LA PALS tertile had a significantly higher risk of reaching the primary endpoint compared with patients in the highest LA PALS tertile (hazard ratio [HR] 9.802; 95% CI 1.832-52.45; p &amp;lt;0.008). Higher LA PALS and LV GLS (LA PALS HR 0.610 95% CI 0.401-0.926; p 0.02; LV GLS HR 0.638 95% CI 0.418-0.972; p 0.037) were significantly associated with a reduction in reaching the primary endpoint in a multi-variate regression model including clinically relevant traditional and strain-based echocardiographic parameters. Conclusions Lower LA PALS is significantly associated with poorer long-term outcomes in cardiac transplant patients with ACR. Non-invasive LA PALS may be a useful predictor of long-term outcome in patients post cardiac transplantation. Abstract Figure. Survival curves for LA PALS tertiles

A case series of novel coronavirus infection in heart transplantation from 2 centers in the pandemic area in the North of Italy

Non-compaction of ventricular myocardium (NVM), a rare congenital and inherited cardiomyopathy, is characterized by prominent trabeculations and deep intertrabecular recesses in communication with the ventricular cavity.NVM has diverse clinical presentations without specificity, of which the major characteristics are cardiac insufficiency, arrhythmias and thrombosis.Echocardiography and cardiac magnetic resonance imaging are necessary technologies to diagnose NVM.Symptomatic therapy is the only choice for most patients.Furthermore, if medical treatment fails, the heart transplantation could be performed.As a whole, NVM has a high mortality and entirely different prognosis, however, the prognosis of asymptomatic patients is relatively good. Key words: Non-compaction of ventricular myocardium; Cardiac insufficiency; Arrhythmia; Thrombosis

To evaluate the efficacy and safety of simvastatin administered to a group of heart transplant patients receiving triple-drug immunosuppressive therapy. We also assessed the potential pharmacokinetic interaction between simvastatin and cyclosporine by comparing mean plasma concentrations of simvastatin beta-hydroxy acid, the major metabolite of the drug, in a group of heart transplant patients treated with cyclosporine and in a control group of patients who had not received heart transplants. Both groups received long-term (> 6 wk) simvastatin therapy. We monitored hyperlipidemia in 20 hypercholesterolemic heart transplant patients receiving simvastatin 10 mg/d and triple-drug immunosuppressive therapy. Changes in laboratory results before and after 4 months of simvastatin therapy were considered. The same laboratory data were monitored in a control group of 20 nonhypercholesterolemic heart transplant patients who were not treated with simvastatin but were receiving triple-drug immunosuppressive therapy. Plasma concentrations of simvastatin beta-hydroxy acid were measured in 14 hypercholesterolemic patients, 7 of whom had received heart transplants and 7 who had not. The Division of Cardiology and the First Medical Clinic for the clinical study, as well as the Department of Pharmacology for the pharmacokinetic analysis. Forty heart transplant patients and 7 hypercholesterolemic nontransplant patients. Effectiveness of simvastatin was determined by comparing cholesterol and lipoprotein plasma concentrations in 20 patients who underwent heart transplant and were treated with simvastatin for 4 months. The safety of the drug was determined by analyzing changes in laboratory results in the treated group and in the control group, both those who had received heart transplants and those who had received immunosuppressive therapy. After 4 months of simvastatin therapy, total cholesterol decreased by 12.5% and low-density lipoprotein cholesterol decreased by 21.3%. The only statistically significant laboratory change was an increase of 28.7% in the alanine aminotransferase concentrations. Plasma concentrations of simvastatin beta-hydroxy acid were higher in heart transplant patients than in those who had not received heart transplants, the control group. Low-dosage simvastatin treatment seems to be safe and sufficiently effective to decrease cholesterol concentrations. Concomitant treatment with immunosuppressive therapy (primarily cyclosporine) in heart transplant patients appeared to cause a reduced metabolic clearance of simvastatin from the plasma. More extensive studies on the interaction between simvastatin and cyclosporine are needed to understand the marked variability found in the response to simvastatin.

Paediatric heart transplantation in children who fail multistage palliation for hypoplastic left heart syndrome is associated with challenges related to immune, clinical or anatomic risk factors. We review current outcomes and risk factors for survival following heart transplantation in this challenging patient population. The United Network for Organ Sharing transplantation database was merged with Paediatric Health Information System database to identify children who received heart transplantation following prior palliation for hypoplastic left heart syndrome. Multivariable Cox analysis of outcomes and factors affecting survival was performed. Our cohort included 849 children between 2009 and 2021. The median age was 1044 days (interquartile range 108-3535), and the median weight was 13 kg (interquartile range 7-26). Overall survival at 10 years following heart transplantation was 71%, with most of the death being perioperative. On multivariable analysis, risk factors for survival included Black race (hazard ratio = 1.630, P = 0.0253), blood type other than B (hazard ratio = 2.564, P = 0.0052) and male donor gender (hazard ratio = 1.367, P = 0.0483). Recipient age, the use of ventricular assist device or extracorporeal membrane oxygenation were not significantly associated with survival. Twenty-four patients underwent retransplantation, and 10-year freedom from retransplantation was 98%. Rejection before hospital discharge and within 1 year from transplantation was 20% and 24%, respectively, with infants having lower rejection rates. Compared with existing literature, the number of children with prior hypoplastic left heart syndrome palliation who receive heart transplantation has increased in the current era. Survival following transplantation in this patient population is acceptable. Most of the death is perioperative. Efforts to properly support these patients before transplantation might decrease early mortality and improve overall survival.

Familial Ebstein's anomaly, left ventricular noncompaction, and ventricular septal defect associated with an MYH7 mutation

Isolated non-compaction of the ventricular myocardium is characterized by numerous and prominent trabeculations and deep intertrabecular recesses. This rare disease is due to an arrest of myocardial morphogenesis. Most cases, when seen in children, are associated with obstructive malformations. Isolated non-compaction is even rarer in childhood, and affects predominantly the myocardium of the left ventricle. Morbidity and mortality resulting from cardiovascular complications is high. In most cases, transplantation is the final option. To our knowledge, this rare cardiac malformation has yet to be diagnosed in the fetus. We report here two sporadic cases, one male and one female, and 2 familial cases, both male, which were diagnosed prenatally and followed by fetal echocardiography. Our study indicates that isolated non-compaction is a primary disorder of early fetal development. Our cross-sectional echocardiographic examinations revealed a fetal cardiomyopathy, with prominent and numerous trabeculations and deep intertrabecular recesses of the myocardium at the apex of the ventricles. In contrast with postnatal experience, we found isolated non-compaction mostly in the right ventricle. Systolic dysfunction was found in all cases. The diagnosis was confirmed by histology in 3 fetuses dying with cardiac failure, and by postnatal cross-sectional echocardiography in the fetus who survived. Two male fetuses belonged to a family in which 3 individuals were subsequently found to be affected. We discuss the issues of prenatal diagnosis, natural history, and myocardial histology.