Cardiac Left Ventricle Mitochondrial Dysfunction After Neonatal Exposure to Hyperoxia: Relevance for Cardiomyopathy After Preterm Birth

Background: Individuals born preterm present left ventricle changes and increased risk of cardiac diseases and heart failure. The pathophysiology of heart disease after preterm birth is incompletely understood. Mitochondria dysfunction is a hallmark of cardiomyopathy resulting in heart failure. We hypothesized that neonatal hyperoxia in rats, a recognized model simulating preterm birth conditions and resulting in oxygen-induced cardiomyopathy, induce left ventricle mitochondrial changes in juvenile rats. We also hypothesized that humanin, a mitochondrial-derived peptide, would be reduced in young adults born preterm. Methods: Sprague-Dawley pups were exposed to room air (controls) or 80% O 2 at postnatal days 3 to 10 (oxygen-induced cardiomyopathy). We studied left ventricle mitochondrial changes in 4 weeks old males. In a cohort of young adults born preterm (n=55) and age-matched term (n=54), we compared circulating levels of humanin. Results: Compared with controls, oxygen-exposed rats showed smaller left ventricle mitochondria with disrupted integrity on electron microscopy, decreased oxidative phosphorylation, increased glycolysis markers, and reduced mitochondrial biogenesis and abundance. In oxygen-exposed rats, we observed lipid deposits, increased superoxide production (isolated cardiomyocytes), and reduced Nrf2 gene expression. In the cohort, left ventricle ejection fraction and peak global longitudinal strain were similar between groups however humanin levels were lower in preterm and associated with left ventricle ejection fraction and peak global longitudinal strain. Conclusions: In conclusion, neonatal hyperoxia impaired left ventricle mitochondrial structure and function in juvenile animals. Serum humanin level was reduced in preterm adults. This study suggests that preterm birth–related conditions entail left ventricle mitochondrial alterations that may underlie cardiac changes perpetuated into adulthood. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03261609.

551 Killip class predictors and prognostic role in acute myocardial infarction

Aims Killip classification is a simple and fast clinical tool for risk stratification in patients with acute coronary syndrome (ACS). However, predictors of high Killip class at admission and its prognostic impact in the clinical contest of myocardial infarction with nonobstructive coronary artery (MINOCA) are still poorly known. To identify the clinical predictors of high Killip class and its potential prognostic role on in-hospital and follow-up outcomes in patients with MINOCA compared to patients with myocardial infarction with obstructive coronary artery (MIOCA). Methods and results We included all consecutive patients with myocardial infarction (MI) undergoing coronary angiogram between 2016 and 2019 at our hospital. According to 2016 ESC Position Paper criteria, we considered as MINOCA all patients with acute MI and with the angiographic conventional cut-off of < 50% coronary stenosis without clinically apparent alternative diagnosis (e.g. sepsis, stroke, pulmonary embolism, myocarditis, and Tako-tsubo). We analysed Killip class of MINOCA patients comparing with those of MIOCA (coronary stenosis ≥50%). Kaplan–Meier (KM) curves were developed for the comparison of overall-mortality among MINOCA with high Killip class (major than 1) compared to other. Multivariate logistic regression analysis was used to determine the predictors of high Killip class both in the MINOCA and MIOCA populations. Among 3165 MI, 260 patients fulfilled the 2016 ESC criteria for MINOCA. Overall, 62.3% were males and the mean age was 68.6 ± 13.2 years. The median follow-up time was 23.3 ± 14.5 months. Killip class >1 occurred in 24 patients in MINOCA group and 507 in MIOCA group (17.5% vs. 9.2%, P = 0.001). The KM survival distributions were significantly different across Killip class >1 (P < 0.001) in both populations with higher mortality in patients with higher Killip class. Finally, the multivariate logistic regression showed that the predictors of high Killip class at time of presentation in MIOCA population were older age [odds ratio: 1.04, 95% CI: (1.03–1.06), P < 0.001], diabetes [odd ratio 0.63, 95% CI (0.48–0.81), P < 0.001], ST elevation [odds ratio: 0.65, 95% CI (0.48–0.89), P = 0.008], left ventricle ejection fraction [odds ratio: 0.95, 95% CI (0.94–0.96), P < 0.001], and elevated cardiac troponin [odds ratio: 1.00, 95% CI (1.00–1.00), P = 0.01]. Older age [odds ratio: 1.08, 95% CI (1.03–1.14), P = 0.003], ST elevation [odd ratio 0.14, 95% CI (0.02–0.93), P = 0.042], and diabetes [odd ratio 3.60, 95% CI (1.08–1.96), P = 0.037] were predictors of high Killip class in MINOCA, however left ventricle ejection fraction (P = 0.3) and elevated cardiac troponin (P = 0.6) did not predict the high Killip class in MINOCA patients. Conclusions Our data suggest that Killip classification performed at the time of admission is a useful clinical marker of a high risk of early and late adverse cardiovascular events even in patients with MINOCA. The predictors of the high Killip class at time of presentation in MIOCA were older age, diabetes, ST elevation, left ventricle ejection fraction, and elevated cardiac troponin. Older age, ST elevation, and diabetes were predictors of high Killip class even in MINOCA, however left ventricle ejection fraction and elevated cardiac troponin did not predict the high Killip class in MINOCA patients. These results could reflect the different pathogenetic myocardial damage in MINOCA and MIOCA populations. Further studies are needed to evaluate these pathological mechanisms.

107 Left ventricular intramural haematoma secondary to transcatheter aortic valve replacement

An 80-year-old woman was electively hospitalized at our institution to undergo transcatheter aortic valve replacement (TAVR) for severe aortic valve stenosis symptomatic for exertional dyspnoea (NYHA III). At the admission she presented a normal electrocardiogram (EKG), a creatinine clearance (CrCl) of 36 ml/min, a normal size and hypertrophic left ventricle with a preserved ejection fraction (EF 70%). A pre-procedure coronary angiography was performed and showed absence of significant epicardic stenoses. A balloon-expandable valve (Edwards Sapien 26 mm) was successfully implanted via the trans-femoral access without intra-procedural complication and the patient was transferred to cardiology ward for monitoring; in the post-procedure, the patient complained of nausea and a feeling of vomiting, without other cardiologic symptoms; she had low blood pressure (BP 95/70 mmHg) with normal heart rate and oxygen saturation (Killip 1). An EKG was performed and showed a ST-elevation in antero-lateral leads, so a bed-side echocardiogram was performed showing a good function of TAVR but an ipo-akinesia of the left ventricle’s lateral wall. The patient was transferred to the Cath lab and at the emergent coronary angiography no clear epicardic stenoses were seen, with a diffuse narrowing of an early obtuse marginal (OM) branch and of the distal branches of circumflex artery, suggestive for a spasm, that was refractory to repeated nitroglycerine infusions. A clear mismatch between coronary angiogram findings and EKG was detected. Considering the hemodynamic compromise and symptoms persistence a percutaneous transluminal coronary angioplasty of OM was performed with a partial ST resolution. The patient was transferred to the Coronary Unit Care where an echocardiogram was repeated confirming the good function of TAVR but outlining the presence of a voluminous intramural haematoma (>30 mm of maximum diameter) with anterior, lateral and posterior wall akinesia and depressed left ventricle ejection fraction (EF 35%). A conservative management of the haematoma was chosen. The hospital stay was complicated by an acute pulmonary oedema, requiring non-invasive ventilation, a cardiogenic shock, requiring inotropic (dobutamine) support, and an acute renal failure (creatinine peak 2.9 mg/dl with CrCl of 15 ml/min) with anuria, requiring continuous renal replacement therapy for two days; she developed a left branch block with no complete atrioventricular block. The pre-discharged echocardiogram showed a partially organized moderate pericardial effusion (1.3 cm) and moderate mitral regurgitation. After six months, she was asymptomatic, with a significant improvement of functional status (NYHA II) and a stable renal function (CrCl > 30 ml/min); no more echocardiographic signs of pericardial effusion were shown but the persistence of akinesia of the postero-lateral- and anterior-wall with depressed left ventricle ejection fraction (EF 37%) and moderate-severe mitral regurgitation. The persistence of good result of TAVR (aortic mean gradient 9 mmHg, absence of peri-valvular leak) was confirmed. Intramural dissecting haematoma (IDH) is a rare complication of myocardial infarction, chest trauma and percutaneous interventions; it consists of a cavity filled with blood, with the integrity of both the outer wall (myocardium and pericardium) and the inner wall (myocardium and endocardium) and it can develop in the left ventricle free wall, the right ventricle and the interventricular septum. IDH’s formation may result from intra-myocardial vessels’ rupture in the interstitial space. Never understimate nausea as symptom: think about heart is challenging but mandatory!

549 The role of conventional and speckle tracking echocardiography in the evaluation of leadless endocardial pacing with Micra-AV

Aims Micra-AV pacing system is a leadless pacemaker (LP) implanted in the right ventricle which can provide atrio-ventricular (AV) synchronous pacing. Echocardiographic data assessing left ventricle contractility 24–48 h after Micra AV implantation are lacking. To evaluate via conventional echocardiography and speckle-tracking echocardiography (STE), which was the best pacing modality (VVI vs. VDD) able to ensure the most efficient hemodynamic performance assessed by left ventricle ejection fraction (LF-EF) and global longitudinal strain (GLS). Methods and results We studied nine patients with high degree AV-block, enrolled in our Institution in a range of time of 5 months. All patients had first degree AV block (PQ interval between 160 and 340 ms). They were considered suitable candidates for MICRA-AV implantation according to current guidelines. Both LF-EF and GLS were performed 24–48 h after device implantation by two experienced echocardiographic physicians. The mean age of the population was 79 ± 8 years (8 were male, 89%). Risk factors more represented were hypertension and dyslipidaemia. The maximum PQ interval was 256 ± 51 ms. VDD pacing modality allows better LV-EF values than those obtained with a VVI stimulation (with a difference that was statistically significant difference, P-value = 0.008). Similarly, we obtained better GLS values during VDD pacing as respect to VVI (P-value = 0.008). Conclusions Left ventricle ejection fraction and LV-GLS improve early after leadless MICRA-AV implantation during VDD as compared to VVI pacing modality.

Non-Invasive Assessment of Left Ventricle Ejection Fraction: Where Do We Stand?

The left ventricular (LV) ejection fraction (EF) is the preferred parameter applied for the non-invasive evaluation of LV systolic function in clinical practice. It has a well-recognized and extensive role in the clinical management of numerous cardiac conditions. Many imaging modalities are currently available for the non-invasive assessment of LVEF. The aim of this review is to describe their relative advantages and disadvantages, proposing a hierarchical application of the different imaging tests available for LVEF evaluation based on the level of accuracy/reproducibility clinically required.

The arch-like plasty of the left atrium in correction of a mitral valve failure

Objective. Studying the possibilities of the method of the left atrium arch-like plasty while correcting of a mitral failure in combination with the left atrium dilatation. Materials and methods. Into the analysis of the surgical treatment results in 190 patients, suffering mitral failure in combination with the left atrium dilatation, who were operated in the National Institute of Cardio-Vascular Surgery named after N. M. Amosov NAMS of Ukraine in a period from 01.01.2012 to 01.01.2021 yr, were included. The main group consisted of 103 patients, to whom correction of a mitral failure in combination with original procedure of the arch-like plasty of left atrium was performed. Into a control group 87 patients were included, to whom the correction of a mitral valve failure was done without concomitant plasty of left atrium. Results. Of 103 operated patients of the main group on the hospital stage 1 have died (0.9% lethality). Dynamics of echocardiographic indices on the treatment stages was following: definitely-systolic index of the left ventricle - (63.1 ± 11.3) ml/m2 (preoperatively), (58.3 ± 8.4) ml/m2 (postoperatively), (49.4 ± 9.2) ml/m2 (remote period); the left ventricle ejection fraction: 0.52 ± 0.04 (preoperatively), 0.55 ± 0.04 (postoperatively), 0.57 ± 0.03 (remote period). Diameter of left atrium: (58.8 ± 6.4) mm (preoperatively), (41.4 ± 5.3) mm (postoperatively), (43.9 ± 2.3) mm (remote period). Sinus rhythm in a remote period was stable in 75 (78.9%) of 95 patients. Of 87 operated patients of a control group 2 died (lethality 2.3%). Dynamics of the echocardiographic indices on the treatment stages was following: definitely-systolic index of left ventricle- (67.3 ± 11.3) ml/m2 (preoperatively), (60.4 ± 9.3) ml/m2 (postoperatively), (52.7 ± 7.2) ml/m2 (remote period); the left ventricle ejection fraction: 0.52 ± 0.05 (preoperatively), 0.54 ± 0.05 (postoperatively), 0.54 ± 0.03 (remote period). Diameter of left atrium: (59.5 ± 2.3) mm (preoperatively), (57.5 ± 3.7) mm (postoperatively), (68.5 ± 3.4) mm (in remote period). Sinus rhythm was stable in 18 (22.5%) of 80 patients, followed in the remote period. Conclusion. The arch-like plasty of left atrium is a low-traumatic and effective procedure, leading to significant improvement of the left atrium morphometry and accompanied by low risk for postoperative lethality.

Unraveling diagnostic co-morbidity makeup of each HF category as characteristically derived by ECG- and ECHO-findings, a prevalence analysis

Heart Failure (HF) relies mainly on measurements from Echocardiography, in particular Echo-Findings, to estimate Left Ventricle Ejection Fraction (LVEF) and evaluating structural heart disease criteria. As Echocardiography is not available in primary care, the key structural (heart chamber enlargements) and functional abnormality related measurements are not available precluding the ability to diagnose HF other than through mainly symptomatic means. The opportunity for earlier detection of HF is lost.In this work, we first explore each of the three HF categories, preserved EF, mild-reduced EF, and reduced EF, using various morphological and functional etiology-specific characteristics supported by a literature review and an extensive analysis of a large, dedicated database accumulated over 8 years.We then explore the typical signs and co-morbidities of HF using prevalence analysis to unravel the diagnostic makeup of each HF category as characteristically derived by ECG- and ECHO-findings. From this, we then conduct a principal component analysis (PCA) of the data to interpret patterns of comorbidities, showing groups of comorbidities frequently associated with each other.Lastly, we delve into the role of breakthrough methods for the analysis of bio-signals to replicate common ECHO-findings, as alternatives for detecting and diagnosing HF similarly to Echocardiography, thereby providing a simple device for the effective detection of HF for use in Primary Care.

Clinically Suspected Myocarditis in COVID-19 Patients: Case Series and Review of Literature

We described eleven patients positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The younger age and female gender seem to contribute to poor outcomes possibly. Furthermore, the left ventricle ejection fraction and pro-BNP improvement within the first week of treatment might indicate a good prognosis.

Clinically Suspected Myocarditis in COVID-19 Patients: Case Series and Review of Literature

We described eleven patients positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The younger age and female gender seem to contribute to poor outcomes possibly. Furthermore, the left ventricle ejection fraction and pro-BNP improvement within the first week of treatment might indicate a good prognosis.