Dilated Left Ventricle Research Articles

Le Cœur en Sabot: shape associations with adverse events in repaired tetralogy of Fallot

BackgroundMaladaptive remodelling mechanisms occur in patients with repaired tetralogy of Fallot (rToF) resulting in a cycle of metabolic and structural changes. Biventricular shape analysis may indicate mechanisms associated with adverse events independent of pulmonary regurgitant volume index (PRVI). We aimed to determine novel remodelling patterns associated with adverse events in patients with rToF using shape and function analysis.MethodsBiventricular shape and function were studied in 192 patients with rToF (median time from TOF repair to baseline evaluation 13.5 years). Linear discriminant analysis (LDA) and principal component analysis (PCA) were used to identify shape differences between patients with and without adverse events. Adverse events included death, arrhythmias, and cardiac arrest with median follow-up of 10 years.ResultsLDA and PCA showed that shape characteristics pertaining to adverse events included a more circular left ventricle (LV) (decreased eccentricity), dilated (increased sphericity) LV base, increased right ventricular (RV) apical sphericity, and decreased RV basal sphericity. Multivariate LDA showed that the optimal discriminative model included only RV apical ejection fraction and one PCA mode associated with a more circular and dilated LV base (AUC = 0.77). PRVI did not add value, and shape changes associated with increased PRVI were not predictive of adverse outcomes.ConclusionPathological remodelling patterns in patients with rToF are significantly associated with adverse events, independent of PRVI. Mechanisms related to incident events include LV basal dilation with a reduced RV apical ejection fraction.

Anaesthetic Management of a Peripartum Cardiomyopathy Patient Undergoing Caesarean Section

Peripartum Cardiomyopathy (PPCM), is an uncommon form of heart failure that occurs during the last month of pregnancy or upto five months after delivery. In this condition, the heart chamber enlarges and the muscle weakens. This case report is about a 30- year-old primigravida,with oligohydramnios, at 32.3 weeks of gestation. She visited for a caesarean section, and was diagnosed with PPCM on the basis of clinical findings of growing fatigability, troubled breathing and severe dyspnoea and on echocardiography ejection fraction of 64% with mild mitral regurgitation, moderate dilated left ventricle, tricuspid regurgitation was found. These patients require vigilantanaesthetic intervention for management of painless labour and/or either vaginal or operative delivery. The basic haemodynamic goals should always be kept in mind for favorable maternal as well as foetal outcomewhile selecting the drug dose and mode of anaesthesia. Various studies showed thatboth general and regional anaesthesia can be used with comparable outcomes in PPCM patients undergoing caesarean section. The index patient, who needed a cesarean section, was managed with Combined Spinal-Epidural (CSE) anaesthesia, weighing the risk of increase mortality due to general anaesthesia.

The time administration and cost burden of intravenous immunoglobulin (IVIG) therapy in a 4-year-old girl with Kawasaki disease: A case report

Kawasaki disease (KD) is an acute systemic vasculitis frequently affecting children under five years old. KD can cause severe complications. It can lead to coronary aneurysms in 15-25% of untreated cases. Intravenous immunoglobulin (IVIG) treatment within ten days of initial onset can reduce the rate of coronary artery aneurysms. However, IVIG administration in Indonesia is currently limited due to its high cost. The case reported a 4-year-old girl with a chief complaint of fever. She complained about a high fever seven days before hospitalization. She also complained about vomiting, cough, joint pain, diarrhea, skin peeling, and rash on her body, palms, and soles. On examination, she looked irritable and sluggish. The temperature was 39.9o C. There were red eyes without discharge, strawberry tongue, oral thrush, and red, dry, cracked lips, swollen neck lymph nodes, and skin rash on her body, palms, and soles. Laboratory testing showed microcytic hypochromic anemia with Hb 7.9 g/dL and leukocytosis 24.230/mm3. Chest X-ray showed perihilar and paracardial infiltrates. Electrocardiogram revealed sinus tachycardia. An echocardiogram showed left ventricle dilatation with trivial mitral regurgitation and no coronary abnormalities were found. She was diagnosed with Kawasaki Disease. She was treated by IVIG 30 gr single dose during 12 hours on day 7 of initial onset, methylprednisolone injection 10 mg/8 hours, paracetamol 150 mg/8 hours, and aspirin 400 mg/8 hours orally and discharged from the hospital with improvement. There weren’t any coronary artery abnormalities found. IVIG administration within ten days of initial onset in KD patients can reduce the risk of coronary artery complications. IVIG administration after day 10 of initial onset can achieve resolution of inflammation but can be insufficient for preventing coronary artery lesions (CALs).

406 A 50 years old man with a late presentation of arrhythmogenic cardiomyopathy

Abstract In January 2014 a 50 years old man without previous medical history experienced a syncopal episode. During evaluation at Emergency department (ED) a sustained ventricular tachycardia (VT) with haemodynamic compromise was found and successfully treated with DC shock. The patient was admitted to the Coronary Care Unit (CCU) where the ECG showed diffuse low QRS voltages and flattened T waves. Coronary angiography showed normal coronary arteries. 2-D echocardiogram documented the presence of a mildly dilated left ventricle (LV) with a mildly decreased systolic function (EF : 41%); the right ventricle (RV) was severely dilated (REDV : 41 cmq/mq) with a severe systolic dysfunction (fractional area change: 21%) with diffuse hypokinesia and akinesia of subtricuspid region. Cardiac magnetic resonance (CMR) confirmed ventricular dimensional and kinetic abnormalities and tissue characterization sequences demonstrated the presence of fatty infiltration of the epicardial segments of LV lateral wall and of RV free wall. After gadolinium injection, late gadolinium enhancement (LGE) presented the same distribution of the fatty infiltration. A diagnosis of arrhythmogenic cardiomyopathy (AC) was made and ICD in secondary prevention was implanted. The patient was treated with Sotalol (240 mg/daily) and remained asymptomatic and free from sustained ventricular arrhythmias for five years. In January 2019 he started to complain asthenia, dyspnoea (NYHA II) and anorexia and he was admitted to ED where a persistent slow VT was detected. Echocardiogram showed a severely dilated LV with severe systolic dysfunction (EF: 30%) with substantially unchanged RV features. One year later he experienced an heart failure (HF) episode with further reduction of LV systolic function (EF: 21%). Cardiopulmonary test documented a severe ventilation/perfusion mismatch (VE/VCO2 slope 50.6) and severe reduction of the exercise tolerance (VO2 peak 9.2 ml/kg/min). In March 2021 the patient started heart transplantation check list. Three weeks after the discharge he was transplanted. In conclusion, this clinical case highlights an infrequent late presentation of AC, with an initial high arrhythmic burden and a following rapid progression to refractory HF requiring heart transplantation.

Myocardial strain measured via two-dimensional speckle-tracking echocardiography in a family diagnosed with arrhythmogenic left ventricular cardiomyopathy

BackgroundArrhythmogenic cardiomyopathy is a myocardial disorder characterized by ventricular arrhythmias, right and/or left ventricular involvement, and fibrofatty infiltrations in the myocardium. We report a family diagnosed with arrhythmogenic left ventricular cardiomyopathy (ALVC) and depict their echocardiographic characteristics.Methods and resultsFifteen family members were divided into three groups based on whether they carried the TMEM43 mutation and had been diagnosed with ALVC. Eight of them had TMEM43 mutations, and four were diagnosed with ALVC according to the Padua criteria. Only the proband experienced sudden cardiac death and had a dilated left ventricle. Left ventricular ejection fraction was reduced in two patients; however, left ventricular global longitudinal strain was depressed in three patients. Low QRS voltages in limb leads were evident in three patients, and five patients had frequent ventricular premature contractions. Late gadolinium enhancement was evident in three patients. Left ventricular layer-specific strain showed that the transmural strain gradient ratio was increased in patients diagnosed with ALVC, and it was elevated in the genotype-positive and phenotype-negative groups compared with healthy individuals.ConclusionGlobal left ventricular longitudinal strain better evaluated left ventricular function than left ventricular ejection fraction. The transmural strain gradient ratio was elevated in patients diagnosed with ALVC, suggesting that it was useful for the evaluation of ALVC.

Changes in Thyroid Hormone Signaling Mediate Cardiac Dysfunction in the Tg197 Mouse Model of Arthritis: Potential Therapeutic Implications.

Background Rheumatoid Arthritis (RA) patients show a higher risk of heart failure. The present study investigated possible causes of cardiac dysfunction related to thyroid hormone (TH) signaling in a RA mouse model. Methods A TNF-driven mouse model of RA[TghuTNF (Tg197)] was used. Cardiac function was evaluated by echocardiography. SERCA2a and phospholamban protein levels in left ventricle (LV) tissue, thyroid hormone levels in serum, TH receptors in LV and TH-related kinase signaling pathways were measured. T3 hormone was administered in female Tg197 mice. Results We show LV and atrial dilatation with systolic dysfunction in Tg197 animals, accompanied by downregulated SERCA2a. We suggest an interaction of pro-inflammatory and thyroid hormone signaling indicated by increased p38 MAPK and downregulation of TRβ1 receptor in Tg197 hearts. Interestingly, female Tg197 mice showed a worse cardiac phenotype related to reduced T3 levels and Akt activation. T3 supplementation increased Akt activation, restored SERCA2a expression and improved cardiac function in female Tg197 mice. Conclusions TNF overexpression of Tg197 mice results in cardiac dysfunction via p38 MAPK activation and downregulation of TRβ1. Gender-specific reduction in T3 levels could cause the worse cardiac phenotype observed in female mice, while T3 administration improves cardiac function and calcium handling via modified Akt activation.

Abstract 10566: Echocardiographic Predictors of Successful Transcatheter Mitral Valve Repair with the Mitraclip System

Introduction: Residual mitral regurgitation (rMR) and elevated transmitral gradients (TMG) are associated with worse outcomes after percutaneous mitral repair. This study aims to assess if pre-intervention MR jet width and its relation to the mitral commissural length (MCL) are able to predict post-procedure rMR and TMG. Methods: Preprocedural echocardiographic images were retrospectively reviewed in 74 patients who underwent an edge-to-edge repair (2014-2018). Maximal MR jet width and MCL were measured from a bi-commissural view. Complete follow-up echocardiographic examination was performed at 1-3 months. Left ventricle (LV) and left atrial (LA) severe dilation were defined as LV end-diastolic diameter ≥6.5 cm and LA indexed volume ≥48 ml/m 2 . Presence of rMR ≥moderate, combination of rMR and TMG >5 mmHg (rMR+TMG), and all-cause mortality within 1-year follow-up were examined. Results: Of 74 patients, 25 (34%) had rMR [17/25 moderate and 8/25 severe)] and 39 (53%) had either rMR or elevated TMG. Both MR jet width and its ratio with MCL were good predictors for the implantation of >2 clips (p<0.01 for both). Patients with rMR had a significantly larger pre-procedural jet width versus those without MR (1.63±0.54 cm vs 1.29±0.53 cm; p=0.01); without significant difference for the ratio of jet width/MCL (p=0.07). However, this ratio was higher in patients having rMR+TMG (41.05±13.15 % vs 34.26±12.64 %; p=0.03). In univariate analysis, MR jet width was a good predictor of rMR (OR: 3.35, 95%CI: 1.09-10.48; p=0.03) and severe post-intervention LV (OR: 6.43, 95%CI: 1.35-45.01; p=0.03) and LA dilation (OR: 3.02, 95%CI: 1.16-8.69; p=0.03); whereas the ratio was a good predictor of rMR+TMG (OR: 1.69, 95%CI: 1.12-2.70; p=0.02). Patients with rMR and rMR+TMG tended to be at higher risk of mortality at one year, without reaching statistical significance in this small population (24% vs 14%, p=0.17 and 23% vs 11%, p=0.14 respectively). Conclusion: MR jet width and its ratio with MCL are respectively associated to rMR or combined rMR+TMG after percutaneous mitral repair. MR jet width was also useful to identify patients who remained with severe LV and LA dilatation post-intervention.

Abstract 17228: Not Just Another Knick In The Wall: An Unusual Case Of Multiple Arterial Aneurysms

Case Presentation: 47-year-old Liberian woman with a history of latent TB and no prior cardiac history presented with dyspnea, palpitations, and weight loss. She had fevers, tachycardia, and cervical lymphadenopathy. Cardiac exam showed widened pulse pressure, systolic and diastolic murmur, and features of heart failure. TTE showed dilated left ventricle with preserved ejection fraction, aortic root aneurysm compressing left atrium, severe aortic and mitral regurgitation, and moderate pericardial effusion with no tamponade. CT angiogram of neck, chest and abdomen showed right subclavian artery mycotic aneurysm, large left supraclavicular lymphadenopathy, multiple aortic arch, and descending thoracic aorta mycotic aneurysms. She underwent emergent surgical intervention. Intraoperative TEE revealed rupture of aortic root aneurysm into left ventricular outflow tract causing a fistula, perforated anterior mitral leaflet, and distortion of the left atrial wall. She underwent mitral and aortic tissue valve replacement, aortic root replacement, and a pericardial patch repair of the left atrial wall. Subsequently, she underwent right subclavian artery aneurysm resection, right carotid axillary bypass, and vertebral artery reimplantation. Aortic valve pathology was suggestive of endocarditis with negative cultures. Lymph node biopsy revealed non-necrotizing granulomatous inflammation with no evidence of acid-fast bacilli, fungi, and malignancy. Autoimmune workup was negative. A PET CT showed post-surgical inflammatory changes with no evidence of malignancy. Discussion: We describe an unusual case of multiple large arterial aneurysms causing severe valvular insufficiency requiring emergent surgical intervention. The patient underwent extensive workup which was unrevealing. She was treated for subacute bacterial endocarditis and suspected Bechet’s disease. Thus, the quest for a definitive diagnosis continues to elude us.

Abstract 11693: When a Parachute Fails: A Rocky Landing to Heart Transplant

A 71 year-old man with heart failure, porcelain aorta, and mitral regurgitation presented for heart transplant evaluation. He was in cardiogenic shock requiring inotropic support. An echocardiogram showed a dilated left ventricle, severely reduced systolic function, restricted mitral valve leaflet motion, an elevated mean transmitral gradient, and severe mitral regurgitation. The differential of mixed stenotic and regurgitant mitral valve pathology included rheumatic heart disease and congenital mitral valve anomaly. Hemodynamic management of cardiogenic shock in the setting of mixed mitral valve disease presented unique challenges due to a narrow therapeutic window of optimal preload, afterload reduction, inotropic support, and chronotropic control. He was not a candidate for percutaneous mitral valve interventions or surgery. A porcelain aorta made him high risk for vascular complications with mechanical circulatory support. His course was complicated by worsening shock requiring escalation of inotropes, rapid atrial fibrillation, and recurrent episodes of acute pulmonary edema. Ultimately, he underwent an orthotropic heart transplant. A transesophageal echocardiogram at the time of transplant suggested a parachute mitral valve, where all chordae appeared be originating from one papillary muscle. However, additional views revealed the presence of two papillary muscles with asymmetric, shortened anterior chordae and a hypertrophied anterior papillary muscle. Findings were consistent with a rare parachute-like asymmetric mitral valve complicated by mild mitral stenosis and severe mitral regurgitation. Examination of the explanted native heart confirmed these findings.This case highlights: 1) complex management of mixed valvular disease in the setting of cardiogenic shock, 2) echocardiographic evaluation of mixed valvular heart disease, and 3) a rare congenital malformation of a parachute-like mitral valve presenting in adulthood.

Protein tyrosine phosphatase receptor-ζ1 deletion triggers defective heart morphogenesis in mice and zebrafish.

Protein tyrosine phosphatase receptor-ζ1 (PTPRZ1) is a transmembrane tyrosine phosphatase receptor highly expressed in embryonic stem cells. In the present work, gene expression analyses of Ptprz1−/− and Ptprz1+/+ mice endothelial cells and hearts pointed to an unidentified role of PTPRZ1 in heart development through the regulation of heart-specific transcription factor genes. Echocardiography analysis in mice identified that both systolic and diastolic functions are affected in Ptprz1−/− compared with Ptprz1+/+ hearts, based on a dilated left ventricular (LV) cavity, decreased ejection fraction and fraction shortening, and increased angiogenesis in Ptprz1−/− hearts, with no signs of cardiac hypertrophy. A zebrafish ptprz1−/− knockout was also generated and exhibited misregulated expression of developmental cardiac markers, bradycardia, and defective heart morphogenesis characterized by enlarged ventricles and defected contractility. A selective PTPRZ1 tyrosine phosphatase inhibitor affected zebrafish heart development and function in a way like what is observed in the ptprz1−/− zebrafish. The same inhibitor had no effect in the function of the adult zebrafish heart, suggesting that PTPRZ1 is not important for the adult heart function, in line with data from the human cell atlas showing very low to negligible PTPRZ1 expression in the adult human heart. However, in line with the animal models, Ptprz1 was expressed in many different cell types in the human fetal heart, such as valvar, fibroblast-like, cardiomyocytes, and endothelial cells. Collectively, these data suggest that PTPRZ1 regulates cardiac morphogenesis in a way that subsequently affects heart function and warrant further studies for the involvement of PTPRZ1 in idiopathic congenital cardiac pathologies.NEW & NOTEWORTHY Protein tyrosine phosphatase receptor ζ1 (PTPRZ1) is expressed in fetal but not adult heart and seems to affect heart development. In both mouse and zebrafish animal models, loss of PTPRZ1 results in dilated left ventricle cavity, decreased ejection fraction, and fraction shortening, with no signs of cardiac hypertrophy. PTPRZ1 also seems to be involved in atrioventricular canal specification, outflow tract morphogenesis, and heart angiogenesis. These results suggest that PTPRZ1 plays a role in heart development and support the hypothesis that it may be involved in congenital cardiac pathologies.

MicroRNAs as Biomarkers in Hypertrophic Cardiomyopathy: Current State of the Art.

Hypertrophic Cardiomyopathy (HCM) is the most common inherited Cardiomyopathy. The hallmark of HCM is myocardial fibrosis that contributes to heart failure, arrhythmias and sudden cardiac death. Currently, there are no reliable serum biomarkers for the detection of myocardial fibrosis, while cardiac magnetic resonance (CMR) is an imaging technique to detect myocardial fibrosis. MicroRNAs (miRNAs) have been increasingly suggested as biomarkers in cardiovascular diseases. However, in HCM there is as yet no identified and verified specific circulating miRNA signature. We conducted a review of the literature to identify the studies that indicate the possible roles of miRNAs in HCM. From studies in transgenic mice with HCM, miR-1, -133 may identify HCM in the early asymptomatic phase. Human miR-29a could be used as a circulating biomarker for detection of both myocardial hypertrophy and fibrosis in HCM, while it could also have a possible additional role in discrimination of hypertrophic obstructive cardiomyopathy from non-obstructive HCM. Additionally, miR-29a-3p is associated with diffuse myocardial fibrosis in HCM, while miR-1-3p could discriminate end-stage HCM from dilated cardiomyopathy and left ventricle dilation. Another role of miRNAs could also be the contribution in the differential diagnosis between HCM and phenocopies. Moreover, miRNA- targeted therapy (miR-133 mimics) is promising in inhibiting cardiac hypertrophy, but this is still in the early stages. A more reliable and specific signature of miRNAs is expected with forthcoming studies in samples from HCM patients and correlation of miRNAs with CMR and serum markers of fibrosis may implicate novel diagnostic and therapeutic pathways.

Ultrastructural Adaptation of the Cardiomyocyte to Chronic Mitral Regurgitation.

Introduction: Mitral regurgitation (MR) imposes volume overload on the left ventricle (LV) and elevates wall stress, triggering its adverse remodeling. Pronounced LV dilation, minimal wall thinning, and a gradual decline in cardiac ejection fraction (EF) are observed. The structural changes in the myocardium that define these gross, organ level remodeling are not known. Cardiomyocyte elongation and slippage have both been hypothesized, but neither are confirmed, nor are the changes to the cardiomyocyte structure known. Using a rodent model of MR, we used immunohistochemistry and transmission electron microscopy (TEM) to describe the ultrastructural remodeling of the cardiomyocyte.Methods: Twenty-four male Sprague-Dawley rats (350–400 g) were assigned to two groups: group (1) rats induced with severe MR (n = 18) and group (2) control rats that were healthy and age and weight matched (n = 6). MR was induced in the beating heart using a 23-G ultrasound-guided, transapical needle to perforate the anterior mitral leaflet, and the rats were followed to 2, 10, and 20 weeks (n = 6/time-point). Echocardiography was performed to quantify MR severity and to measure LV volume and function at each time-point. Explanted myocardial tissue were examined with TEM and immunohistochemistry to investigate the ultrastructural changes.Results: MR induced rapid and significant increase in end-diastolic volume (EDV), with a 50% increase by 2 weeks, compared with control. Rise in end-systolic volume (ESV) was more gradual; however, by 20 weeks, both EDV and ESV in MR rats were increased by 126% compared with control. A significant decline in EF was measured at 10 weeks of MR. At the ultrastructural level, as early as 2 weeks after MR, cardiomyocyte elongation and increase in cross-sectional area were observed. TEM depicted sarcomere shortening, with loss of Z-line and I-band. Desmin, a cytoskeletal protein that is uniformly distributed along the length of the cardiomyocyte, was disorganized and localized to the intercalated disc, in the rats induced with MR and not in the controls. In the rats with MR, the linear registry of the mitochondrial arrangement along the sarcomeres was lost, with mitochondrial fragmentation, aggregation around the nucleus, and irregularities in the cristae.Discussion: In the setting of chronic mitral regurgitation, LV dilatation occured by cardiomyocyte elongation, which manifests at the subcellular level as distinct ultrastructural alterations of the sarcomere, cytoskeleton, and mitochondria. Since the cytoskeleton not only provides tensegrity but has functional consequences on myocyte function, further investigation into the impact of cytoskeletal remodeling on progressive heart failure or recovery of function upon correcting the valve lesion are needed.

Relationship of Mechanical Dyssynchrony and LV Remodeling With Improvement of Mitral Regurgitation After CRT

ObjectivesThe aim of this study was to explore the association between mechanical dyssynchrony of the left ventricle before cardiac resynchronization therapy (CRT) and improvement of mitral regurgitation (MR) after CRT. BackgroundMR is very frequent among patients with dilated cardiomyopathy and conduction delay. MethodsEchocardiograms (pre-CRT and 12 ± 3.8 months thereafter) of 314 patients with dilated cardiomyopathy and any degree of MR, who underwent CRT device implantation according to guidelines, were analyzed. Left ventricular (LV) mechanical dyssynchrony was assessed by apical rocking (ApRock) and septal flash (SF), while MR severity was graded from I to IV on the basis of vena contracta width, regurgitation jet size, and proximal isovelocity surface area. ResultsAt baseline, 30% of patients presented with severe MR (grade III or IV). In 62% of patients, MR decreased after CRT, and these patients more frequently had left bundle branch block, had more severe MR, had more dilated left ventricles, had lower ejection fractions, and more often had ApRock and SF. Reverse remodeling was more frequent among patients with MR reduction (ΔLV end-systolic volume −35.5% ± 27.2% vs −4.1% ± 33.2%; P < 0.001). In a multivariable logistic stepwise regression, only ApRock (odds ratio [OR]: 3.8; 95% CI: 1.7-8.5; P = 0.001), SF (OR: 3.6; 95% CI: 1.6-7.9; P = 0.002), and baseline MR (OR: 1.4; 95% CI: 1.0-1.9; P = 0.046) remained significantly associated with MR reduction. ConclusionsApRock, SF, and severity of MR at baseline are strongly associated with MR reduction after CRT, while LV reverse remodeling is its underlying mechanism. Therefore, in patients with heart failure with LV dyssynchrony on optimal medical treatment, CRT should be the primary treatment attempt for relevant MR.

Updated results of hybrid transcatheter and minimally invasive left ventricular reconstruction for the treatment of ischemic cardiomyopathy

Abstract Aims Remodelling of the left ventricle (LV) after anterior myocardial infarction can result in a pathological increase in LV volume and reduction in LV ejection fraction (EF). We describe the updated results of an l hybrid transcatheter and minimally invasive surgical technique to reconstruct the negatively remodelled LV by myocardial scar plication and exclusion to rehape and reduce the excess volume, decrease the wall stress and increase LVEF. Methods and results Patients were considered eligible for the procedure when they presented with symptomatic heart failure (NYHA-class ≥II or more) and ischemic cardiomyopathy (EF&amp;lt;40%) after anterior myocardial infarction. All patients had a dilated LV with either a- or dyskinetic scar in the anteroseptal wall and/or apex of ≥50% transmurality. Hybrid transcatheter and minimally technique that relies on micro-anchoring technology is used to reconstruct the LV by plication of the fibrous scar. A series of internal and external micro anchors are brought together over a PEEK (poly-ether-ether-ketone) tether to form a longitudinal line of apposition between the LV free wall and the anterior septum from the mid-ventricle to the apex. Internal anchors are deployed by transcatheter technique on the right side of the ventricular septum through the right internal jugular vein. Paired external anchors are advanced through a left sided mini-thoracotomy and deployed on the LV epicardium (figure 1). A specialized Force Gauge is used to bring these “RV-LV” anchors together under measured compression forces. “LV-LV” anchor pairs through the LV apex beyond the distal tip of the RV complete the reconstruction. Between October 2016 and March 2021 28 patients (23 males, 5 females; mean age 61±12 years) were operated in a single Dutch centre. Procedural success was 100%. On average 2.3±0.8 anchor-pairs were used to reconstruct the LV. Comparing echocardiographic data pre- and directly postoperatively, LVEF increased from 33±8% to 44±10% (change +35%, P&amp;lt;0.0001) and LV-volumes decreased: LVESV 116 ml ± 52 ml to 69±39 ml (change −35%, P&amp;lt;0.0001) and LVEDV 170 ml ± 72 ml to 118±55 ml (change −29%, P&amp;lt;0.0001). Hospital mortality was 0%. Also no strokes occurred. Median duration of ICU–stay was 2 days (IQR 1–48 days) and median length of hospital stay was 7 days (IQR 5–61 days). Survival at 48 months was 84%. At latest follow-up, 9670% of surviving patients were in NYHA-class I-II compared to 18% preoperatively. Conclusions Hybrid transcatheter and minimally invasive LV reconstruction is a promising novel treatment option for patients with symptomatic heart failure and ischemic cardiomyopathy after anteroseptal myocardial infarction. Updated results demonstrate that the procedure is safe and results in significant improvement in EF, reduction in LV volumes and sustained improvement in heart failure symptoms. Funding Acknowledgement Type of funding sources: None. Figure 1

Reverse remodelling criteria to predict cardiovascular death in heart failure with reduced or mid-range ejection fraction

Abstract Aims Reverse remodelling (RR) is the recovery from left ventricle (LV) dilatation and dysfunction. There are no established definitions of RR. We sought to identify RR criteria that better predicted cardiovascular death. Methods and results Forty-two studies used 25 criteria to define RR, most commonly (n=12) as LV end-systolic volume (LVESV) reduction ≥15%. We evaluated 927 patients with LV ejection fraction (LVEF) &amp;lt;50% undergoing 2 echocardiograms within 12±2 months. Over a median 2.8-year follow-up after the second echocardiogram (1.3–4.9), 123 cardiovascular deaths occurred (13%). Model 1 included age, LVEF, N-terminal pro-B-type natriuretic peptide (NT-proBNP), ischaemic aetiology, cardiac resynchronization therapy (CRT), estimated glomerular filtration rate (eGFR), New York Heart Association (NYHA), and LVESV index (LVESVi), and Model 2 the validated 3C-HF score. Two RR criteria proved particularly effective in risk reclassification over Model 1 and Model 2: LVEF increase ≥1 category (severe [LVEF ≤30%], moderate [LVEF 31–40%], mild LV dysfunction [LVEF 41–55%] and normal LV function [LVEF ≥56%]), and LVEF increase &amp;gt;10 U. The same 2 criteria yielded independent prognostic significance and improved reclassification also in patients with LVEF &amp;lt;40% or LVEF ≤35%. LVEF increase ≥1 category and LVEF increase &amp;gt;10 U displayed a stronger prognostic value than LVESV reduction ≥15%, both in the whole population and the subsets with LVEF &amp;lt;40% or ≤35%. Funding Acknowledgement Type of funding sources: None.

Cardiac Scintigraphy and Screening for Transthyretin Cardiac Amyloidosis: Caveat Emptor.

Cardiac Scintigraphy and Screening for Transthyretin Cardiac Amyloidosis: Caveat Emptor.

Diagnosis of Cardiac Involvement in Amyloid A Amyloidosis by Cardiovascular Magnetic Resonance Imaging.

Background: Diagnosis of cardiac involvement in amyloid A (AA) amyloidosis is challenging since AA amyloidosis is a rare disease and cardiac involvement even less frequent. The diagnostic yield of currently available non-invasive imaging methods is not well-studied and rather limited, and invasive endomyocardial biopsy (EMB) is rarely performed due to the potential risk of this procedure. Cardiovascular magnetic resonance (CMR)-based myocardial tissue characterization by late-gadolinium-enhancement (LGE) imaging and novel-mapping approaches may increase the diagnostic yield in AA amyloidosis.Methods: Two patients with AA amyloidosis in whom cardiac involvement was suspected based on CMR findings and subsequently proven by biopsy work-up are presented. CMR studies were performed on a 1.5-T system and comprised a cine steady-state free precession pulse sequence for ventricular function and a late-gadolinium-enhancement (LGE) sequence for detection of myocardial pathology. Moreover, a modified Look-Locker inversion recovery (MOLLI) T1-mapping sequence was applied in basal, mid and apical short-axes prior to contrast agent administration and ~20 min thereafter to determine native T1 and ECV values.Results: Both patients showed slightly dilated left ventricles (LV) with mild to moderate LV hypertrophy and preserved systolic function. Only a very subtle pattern of LGE was observed in both patients with AA amyloidosis. However, markedly elevated native T1 (max. 1,108 and 1,112 ms, respectively) and extracellular volume fraction (ECV) values (max. 39 and 48%, respectively) were measured in the myocardium suggesting the presence of cardiac involvement - with subsequent EMB-based proof of AA amyloidosis.Conclusion: We recommend a multi-parametric CMR approach in patients with AA amyloidosis comprising both LGE-based contrast-imaging and T1-mapping-based ECV measurement of the myocardium for non-invasive work-up of suspected cardiac involvement. The respective CMR findings may be used as gatekeeper for additional invasive procedures (such as EMB) and as a non-invasive monitoring tool regarding assessment and modification of ongoing treatments.

ALPK3 gene-related pediatric cardiomyopathy with craniofacial-skeletal features: a report and literature review

Objective: To explore the clinical characteristics and mutation spectrum of ALPK3-related pediatric cardiomyopathy and craniofacial-skeletal abnormalities in children. Methods: The clinical data during a follow-up of 11 years including clinical features, echocardiogram, electrocardiogram, cardiac magnetic resonance, genetic testing, and other data of a child firstly diagnosed with ALPK3 gene-related cardiomyopathy and craniofacial-skeletal abnormalities in China were collected retrospectively. The literatures containing the keyword of "ALPK3 gene" published in the China National Knowledge Infrastructure, Wanfang database and PubMed were collected up to November 2020. Then, the clinical features and gene mutations of ALPK3 gene-related pediatric cardiomyopathy with craniofacial-skeletal features were summarized. Results: A female patient aged 10 months who presented with an enlarged heart for 2 months, was admitted to the hospital and initially diagnosed with endocardial elastic fibrosis. The echocardiography showed features of dilated left ventricle (LV) and LV systolic dysfunction. Low-set ears, webbed neck, a grade 2/6 systolic murmur at lower left sternal area and bilateral absent flexion creases of dig were observed. After treatment, the size and function of the heart recovered to normal at age 13 months. However, the ventricular septum and LV wall were thicker than normal values. Then, the diagnosis was revised to hypertrophic cardiomyopathy(HCM) and suspected congenital malformation syndrome. LV hypertrophy (LVH) progressed slowly before the age of 8 years and then progressed rapidly. At age 9 years, compound heterozygous ALPK3 mutations (c.721dup, p.Y241Lfs*42(exon 1) and c.4840C>T, p.R1614*(exon 10)) were detected in the proband and the mutations had not been reported previously. Then, the final diagnosis of ALPK3 gene-related pediatric cardiomyopathy with craniofacial-skeletal features was made. During the follow up of 11 years, regular follow-up echocardiographic images showed progressive LVH. At age 11 years, electrocardiogram showed LVH, ST-T changes in multiple-lead, T wave inversion, and prolonged QT intervals. Cardiac magnetic resonance showed biventricular hypertrophy and late gadolinium enhancement showed non-uniform enhancement of left and right ventricular myocardium. A total of 7 articles published in English were retrieved, and no Chinese literature was found. Twenty-eight cases were reported in the articles plus the patient in this study. Twenty-four mutations were reported worldwide, 18 patients carried homozygous mutations and 10 patients compound heterozygous mutations. Eleven patients showed dilated cardiomyopathy (DCM) at early stage of disease, and 10 of them transitioned to HCM at the disease progression stage. Eight patients presented with HCM at early stage of disease. Nine patients initially exhibited a mixed phenotype of DCM and HCM, and 6 of them eventually progressed to HCM. Electrocardiogram showed prolonged QT interval. Extracardiac features included short stature, special face, cleft palate, webbed neck, joint contracture, and scoliosis, etc. Conclusions: Progressive myocardial hypertrophy is a major feature of ALPK3 gene-related cardiomyopathy with craniofacial-skeletal malformations. Precise diagnosis depends on molecular genetic techniques. More cases should be accumulated for further analysis on the genotype-phenotype correlation and prognosis assessment.

Magnetic Resonance Detects Structural Heart Disease in Patients with Frequent Ventricular Ectopy and Normal Echocardiographic Findings.

The prognosis of patients with ventricular ectopy and a normal heart, as evaluated by echocardiography, is virtually unknown. Cardiac magnetic resonance (CMR) can detect focal ventricular anomalies that could act as a possible site of origin for premature ventricular contractions (PVCs). The aim of this study was to investigate the presence of cardiac anomalies in patients with normal findings at echocardiogram. Methods: Fifty-one consecutive patients (23 women, 28 men, mean age 59 years) with very high PVC burden (>10,000 PVC/day) and normal findings at standard echocardiography and exercise test were examined with CMR. The outcome was pathologic findings, defined as impaired ejection fraction, regional wall motion abnormalities, abnormal ventricular volume, myocardial edema and fibrosis. Results: Sixteen out of 51 patients (32%) had structural ventricular abnormalities at CMR. In five patients CMR showed impairment of the left ventricular and/or right ventricular systolic function, and six patients had a dilated left and/or right ventricle. Regional wall motion abnormalities were seen in six patients and fibrosis in four. No patient had CMR signs of edema or met CMR criteria for arrhythmogenic right ventricular cardiomyopathy. Five patients had extra-ventricular findings (enlarged atria in three cases, enlarged thoracic aorta in one case and pericardial effusion in one case). Conclusions: In this study 16 out of 51 patients with a high PVC burden and normal findings at echocardiography showed signs of pathology in the ventricles with CMR. These findings indicate that CMR should be considered in evaluating patients with a high PVC burden and a normal standard investigation.

Effect of Neprilysin Inhibition for Ischemic Mitral Regurgitation after Myocardial Injury.

Angiotensin receptor neprilysin inhibitor (ARNI) treatment reduces functional mitral regurgitation (MR) to a greater extent than angiotensin receptor blocker (ARB) treatment alone, but the mechanism is unclear. We evaluated the mechanisms of how ARNI has an effect on functional MR. After inducing functional MR by left circumflex coronary artery occlusion, male Sprague Dawley rats (n = 31) were randomly assigned to receive the ARNI LCZ696, the ARB valsartan, or corn oil only (MR control). Excised mitral leaflets and left ventricle (LV) were analyzed, and valvular endothelial cells were evaluated focusing on molecular changes. LCZ696 significantly attenuated LV dilatation after 6 weeks when compared with the control group (LV end-diastolic volume, 461.3 ± 13.8 µL versus 525.1 ± 23.6 µL; p < 0.05), while valsartan did not (471.2 ± 8.9 µL; p > 0.05 to control). Histopathological analysis of mitral leaflets showed that LCZ696 strongly reduced fibrotic thickness compared to the control group (28.2 ± 2.7 µm vs. 48.8 ± 7.5 µm; p < 0.05). Transforming growth factor-β and downstream phosphorylated extracellular-signal regulated kinase were also significantly lower in the LCZ696 group. Consequently, excessive endothelial-to-mesenchymal transition (EndoMT) was mitigated in the LCZ696 group compared to the control group and leaflet area was higher (11%) in the LCZ696 group than in the valsartan group. Finally, the MR extent was significantly lower in the LCZ696 group and functional improvement was observed. In conclusion, neprilysin inhibitor has positive effects on LV reverse remodeling and also attenuates fibrosis in MV leaflets and restores adaptive growth by directly modulating EndoMT.