Ventricular Contractility Research Articles

Septic Cardiomyopathy: From Pathophysiology to the Clinical Setting.

The onset of cardiomyopathy is a common feature in sepsis, with relevant effects on its pathophysiology and clinical care. Septic cardiomyopathy is characterized by reduced left ventricular (LV) contractility eventually associated with LV dilatation with or without right ventricle failure. Unfortunately, such a wide range of ultrasonographic findings does not reflect a deep comprehension of sepsis-induced cardiomyopathy, but rather a lack of consensus about its definition. Several echocardiographic parameters intrinsically depend on loading conditions (both preload and afterload) so that it may be challenging to discriminate which is primitive and which is induced by hemodynamic perturbances. Here, we explore the state of the art in sepsis-related cardiomyopathy. We focus on the shortcomings in its definition and point out how cardiac performance dynamically changes in response to different hemodynamic clusters. A special attention is also given to update the knowledge about molecular mechanisms leading to myocardial dysfunction and that recall those of myocardial hibernation. Ultimately, the aim of this review is to highlight the unsolved issue in the field of sepsis-induced cardiomyopathy as their implementation would lead to improve risk stratification and clinical care.

Clinical and laboratory characteristics of patients with paediatric inflammatory multisystem syndrome temporally associated with COVID-19 (PIMS-TS)

Abstract Introduction. Paediatric Inflammatory Multisystem Syndrome Temporally Associated with COVID-19 (PIMS-TS) is a rare complication of SARS-CoV-2 infection in children. There are also problems with the digestive system (vomiting, diarrhea, abdominal pain), conjunctivitis, headaches, swelling of the hands and feet, and others. Aim. The aim of the study is the clinical and laboratory evaluation of patients meeting the PIMS-TS criteria according to the RCPCH. This study aimed to determine the clinical and laboratory characteristics of patients meeting criteria for PIMS-TS. Material and methods. The study was a retrospective analysis of hospital records of 29 PIMS-TS patients of the Provincial Paediatric Hospital in Bydgoszcz hospitalised between November 2020 and August 2021. Results. Fever was found in 100% of the patients. Other symptoms re-ported were gastrointestinal problems, headache, apathy, oral inflammation, and more. Every fourth patient was diagnosed with pulmonary interstitial lesions in the form of smudgy or fine patchy thickening. Echocardiographic tests showed decreased left ventricular contractility in 10 patients. Reduced left ventricular fractional shortening below 28% was found in four patients and ejection fraction below 55% in five patients. In every second child, abdominal ultrasound imaging showed lesions such as enlarged mesenteric lymph nodes, peritoneal effusion, or enlarged liver. Changes were also confirmed by laboratory tests. Conclusions. Patients with PIMS-TS showed increased levels of inflammatory and myocardial dysfunction markers. The long-term prognosis for PIMS-TS is still uncertain. Further research and observation are needed to determine long-term complications and the actual pathomechanisms of the disease.

Treating Dilated Cardiomyopathy with Methylene Blue Using the Drosophila melanogaster Heart Model

Dilated cardiomyopathy (DCM), the most common cardiomyopathy, is characterized by ventricular dilation and impaired heart contractility. Past studies found that the inhibition of the ubiquitin-proteasome system (UPS), a crucial protein degradation system that removes dysfunctional proteins, plays a key role in the pathogenesis of DCM. Since treatments for DCM only aim at alleviating heart failure symptoms, a new therapeutic was sought. Methylene blue (MB) was selected because of its cardioprotective properties and ability to increase proteasome activity, potentially allowing it to revert the impact of an impaired UPS. The Drosophila melanogaster strain wupA, which presents DCM symptoms, was used and treated with MB (30 μM). The flies’ lifespans and negative geotaxis were assessed, and dissections were conducted to analyze heart rates (HR), heart diameters, and fractional shortening (FS) with ImageJ. The log-rank test and t-tests were used to analyze statistical significance. Results showed that DCM increased the heart diameters (p<0.01) and decreased the HR (p<0.05), FS (p<0.01), and negative geotaxis (p<0.01). MB fully restored the dilated heart diameters and impaired FS as there was no significant difference between control and experimental groups (p>0.05), exhibiting potential in treating DCM. However, MB didn't affect the impaired HR and negative geotaxis of flies with DCM. Hence, future studies should investigate supplemental treatments to fully restore those properties.

Evaluation of Fetal Cardiac Geometry and Contractility in Gestational Diabetes Mellitus by Two-Dimensional Speckle-Tracking Technology.

Background: The most commonly known cardiac effect of gestational diabetes mellitus (GD) in the fetus is hypertrophic cardiomyopathy, but recent studies show that it is preceded by subclinical cardiac dysfunction. This study aimed to assess the effect of GD on fetal cardiac geometry and contractility by two-dimensional speckle-tracking technology. Methods: We performed a prospective observational study that included 33 pregnant patients with GD and 30 healthy individuals. For all fetuses, a four-chamber 3 s cine-loop was recorded and analyzed with Fetal Heart Quantification (FetalHQ®), a novel proprietary speckle-tracking software. The following cardiac indices were calculated: global sphericity index (GSI), global longitudinal strain (GLS), fractional area change (FAC), and 24-segment end-diastolic diameter (EDD), fractional shortening (FS), and sphericity index (SI) for both ventricles. Demographic and cardiac differences between the two groups were analyzed, as well as intra-rater and inter-rater reliability. Results: There were significant changes in right ventricular FAC and FS for segments 4–24 in fetuses exposed to GD (−1 SD, p < 0.05). No significant differences were detected for GSI, GLS, EDD, or SI for either ventricle. Conclusions: Fetuses exposed to GD present impaired right ventricular contractility, especially in the mid and apical segments.

Angiotensin-(1−7) attenuates the negative inotropic response to acetylcholine in the heart

Previous studies have suggested that the Angiotensin-(1−7) [(Ang-(1−7)] can change cardiac function by modulating the autonomic nervous system. However, it is unknown whether the Ang-(1−7) can modulate the effect of acetylcholine (ACh) in ventricular contractility. Thus, this study aimed to investigate whether Ang-(1−7) modifies the amplitude of the cardiac cholinergic effects and if these effects are intrinsic to the heart. In anesthetized Wistar rats, Ang-(1−7) attenuated the effect of ACh in decreasing the left ventricular end-systolic pressure (LVESP), dP/dtmax, and dP/dtmin, but did not modify the hypotensive effect of ACh. Similarly, Ang-(1−7) attenuated the reduction of the LVESP, dP/dtmax, and dP/dtmin evoked by ACh in isolated hearts. These effects were blocked by the Mas receptor antagonist, A-779, but not by the adenylyl cyclase inhibitor MDL-12,330 A. Ang-(1−7) also attenuated the reduction in the maximum contraction and relaxation speeds and the shortening promoted by ACh in isolated cardiomyocytes. These data show that Ang-(1−7) acting through Mas receptor counter-regulates the myocardial contractile response to ACh in an arterial pressure and heart rate-independent manner.

Nicorandil attenuates ventricular dysfunction and organ injury after cardiopulmonary bypass

BackgroundNicorandil, an adenosine triphosphate-sensitive potassium channel agonist and nitric oxide donor, is a coronary vasodilator used to treat ischemia-induced chest pain, but it's potential cardioprotective benefits during open heart surgery have not been thoroughly investigated. The study objective was to assess the impact of nicorandil on postoperative ventricular dysfunction and end-organ injury in an established experimental model of open-heart surgery with cardiopulmonary bypass (CPB) and cardioplegic arrest. We hypothesized that nicorandil would attenuate myocardial ischemia-reperfusion (IR) injury, preserve ventricular function, and reduce end-organ injury. MethodsRabbits were cannulated for CPB, followed by 60 min of aortic cross-clamp (ACC) with cold cardioplegic arrest, and 120 min of recovery after ACC removal. Nicorandil (or normal saline vehicle) was given intravenously 5 min before ACC and continued throughout the recovery period. Left ventricular developed pressure (LVDP), systolic contractility (LV + dP/dt), and diastolic relaxation (LV -dP/dt) were continuously recorded, and blood and tissue samples were collected for measurement of oxidant stress (OS), inflammation, apoptosis, and organ injury. ResultsNicorandil significantly attenuated IR-induced LV dysfunction compared to saline control (R-120: LV + dP/dt: 1596 ± 397 vs. 514 ± 269 mmHg/s, p = 0.010; LV -dP/dt: −1524 ± 432 vs. -432 ± 243 mmHg/s, p < 0.001; LVDP: 55 ± 11 vs. 22 ± 5 mmHg, p = 0.046). Furthermore, nicorandil inhibited IR-induced increases in OS, inflammation, apoptosis, and organ injury. ConclusionsNicorandil exhibits myocardial protection by attenuation of IR-induced LV dysfunction associated with OS, inflammation, apoptosis, and organ injury. Nicorandil should be explored further as a potential therapeutic strategy for limiting global IR injury during open-heart surgery in humans.

Early outcomes of valve preservation in patients with ascending aortic aneurysm and bicuspid valve disease

Background: Bicuspid aortic valve (BAV) is the most frequent congenital heart disease affecting 1% to 2% of the population, with thoracic aortic aneurysm (TAA) formation being its second most frequent complication after aortic valve dysfunction (stenosis or insufficiency). Aortic valve replacement (AVR) with mechanical or biologic prostheses has long been the procedure of choice. Although prosthetic AVR is effective in correcting the hemodynamic problem, there are important long-term drawbacks. These are particularly present in a younger patient population, such as the majority of individuals with a BAV. Patient and methods: 40 patients underwent aortic valve repair for bicuspid aortic valve disease with ascending aortic aneurysm in the period between June 2020 and February 2022 in Kasr Alainy hospitals. Results: All our patients showed significant improvement regarding left ventricular dimensions and contractility. Two patients had mild to moderate regurge and thirty eight patients had non-significant regurge in the six month follow up echo. One patient complicated by complete heart block required permanent pacemaker implantation, another two patients had postoperative high drainage required revision for bleeding. One patient died from ventilator associated pneumonia after prolonged mechanical ventilation due to disturbed conscious level.

Scale space detector for analyzing spatiotemporal ventricular contractility and nuclear morphogenesis in zebrafish

SummaryIn vivo quantitative assessment of structural and functional biomarkers is essential for characterizing the pathophysiology of congenital disorders. In this regard, fixed tissue analysis has offered revolutionary insights into the underlying cellular architecture. However, histological analysis faces major drawbacks with respect to lack of spatiotemporal sampling and tissue artifacts during sample preparation. This study demonstrates the potential of light sheet fluorescence microscopy (LSFM) as a non-invasive, 4D (3days + time) optical sectioning tool for revealing cardiac mechano-transduction in zebrafish. Furthermore, we have described the utility of a scale and size-invariant feature detector, for analyzing individual morphology of fused cardiomyocyte nuclei and characterizing zebrafish ventricular contractility.

Deficiency in DDR1 Induces Pulmonary Hypertension and Impaired Alveolar Development.

Pulmonary hypertension (PH) is a multifaceted condition characterized by elevated pulmonary arterial pressure, which can result in right ventricular dysfunction and failure. Disorders of lung development can present with secondary PH, which is a leading cause of mortality in infants with bronchopulmonary dysplasia (BPD). DDR1 (discoidin domain receptor 1) is a collagen-binding receptor that regulates tissue fibrosis and inflammation and controls cellular growth and migration. However, the roles of DDR1 in lung development or the pathogenesis of PH are unknown. Studying mice with a DDR1 deletion (Ddr1-/-), we have noted 35% mortality between 1 and 4 months of age, and we demonstrate that DDR1 deficiency results in reduced right ventricular contractility and muscularization of distal pulmonary arteries, consistent with PH. Pathology analysis revealed enlarged alveolar spaces in Ddr1-/- mice by Postnatal Day 7, consistent with impaired alveolar development. Gene expression analysis showed that Ddr1-/- mice have reduced concentrations of alveologenesis factors and epithelial-to-mesenchymal transition markers. Mechanistic studies invitro confirmed that DDR1 mediated epithelial-to-mesenchymal transition, migration, and growth of alveolar epithelial cells. Taken together, these data suggest that DDR1 plays important roles mediating alveolarization during lung development. Our studies also describe a new model of spontaneous PH and bronchopulmonary dysplasia in mice.

Letter by Li and Nie Regarding Article, “Inflammatory Glycoprotein 130 Signaling Links Changes in Microtubules and Junctophilin-2 to Altered Mitochondrial Metabolism and Right Ventricular Contractility”

HomeCirculation: Heart FailureVol. 15, No. 8Letter by Li and Nie Regarding Article, “Inflammatory Glycoprotein 130 Signaling Links Changes in Microtubules and Junctophilin-2 to Altered Mitochondrial Metabolism and Right Ventricular Contractility” Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBLetter by Li and Nie Regarding Article, “Inflammatory Glycoprotein 130 Signaling Links Changes in Microtubules and Junctophilin-2 to Altered Mitochondrial Metabolism and Right Ventricular Contractility” Ruopu Li, MD, PhD and Yu Nie, PhD Ruopu LiRuopu Li https://orcid.org/0000-0002-7724-018X State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. Search for more papers by this author and Yu NieYu Nie https://orcid.org/0000-0002-8744-0046 State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. Search for more papers by this author Originally published27 Jun 2022https://doi.org/10.1161/CIRCHEARTFAILURE.122.009531Circulation: Heart Failure. 2022;15Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: June 27, 2022: Ahead of Print To the Editor:We read with great interest the recent article by Prisco et al1 regarding the cardiac-protective role of gp130 blockade in monocrotaline induced pulmonary artery hypertension reflected by the antihypertrophy, antifibrotic effect, and the mitigated right ventricle function after gp130 antagonist SC-144 administration. The study expanded our consideration of gp130’s downstream signal to right heart function and its connecting role of inflammation, cytoskeleton organization and energy metabolism. However, here are some questions we would like to raise regarding the findings in the original article.Regenerative repair after myocardial injury requires gp130-induced STAT3 and Src-YAP pathways.2,3 And it has been reported that the loss of gp130 signaling in heart lead to adaption incapacity under biomechanical stress of pressure overload.4 We would like to respectfully ask what is the authors’ perspective on the opposite biological effect of gp130 concerning cardiac tissue response toward stress between left and right ventricle.Although major, there are different pathways downstream of gp130 other than Jak-STAT3. Did the author also detect other signaling pathways, including Erk-MAPK (extracellular regulated protein kinases-mitogen activated protein kinase pathway), PI3K-Akt (phosphoinositide-3 kinase-serine/threonine kinase Akt [also known as protein kinase B or PKB] pathway), and Src-YAP (pathway of proto-oncogene tyrosine-protein kinase Src and its downstream protein Yes associated protein [YAP]) pathways, in the pulmonary artery hypertension model before and after SC-144 administration? And did the author confirm the similar effect with SC-144 treatment under STAT3 antagonized model? SC-144 was adopted for the construction of gp130 depletion model. But the agent triggers different gp130 downstream signaling alteration including STAT3 inhibition and Erk activation.5The author treated immortalized H9c2 cell line with cytoskeleton stabilizer paclitaxel and detected an impaired mitochondrial metabolic activity. Here, we expected whether cytoskeleton interference would result in the same outcome in mitochondrial metabolism in primary neonatal rat ventricular myocytes (primary cardiomyocytes isolated form neonatal Rattus norvegicus). Paclitaxel has cytotoxicity on proliferative cells by inhibiting spindle formation, and cell mitosis is an energy-consuming process. So, the impair of cell cycle results in metabolic dysfunction. It is confusing whether it was due to the cell cycle toxicity or the cytoskeleton stabilizing that causes the alteration of mitochondrial metabolism.Article InformationSources of FundingThis work was supported by the National Natural Science Foundation of China (grant 81970243) and the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (grant 2021-I2M-1-008).Disclosures None.FootnotesFor Sources of Funding and Disclosures, see page 823.

The burden of alcoholic cardiomyopathy in China and different regions around the world.

BackgroundAlcoholic cardiomyopathy (ACM) remains a significant public health issue with a growing global burden. The burden of ACM in China and different regions remains poorly understood.MethodsData on ACM deaths, disability-adjusted life years (DALYs), the corresponding global age-standardized death rate (ASDR), age-standardized DALY rate and estimated annual percentage change (EAPC) were analysed based on age, sex, socio-demographic index (SDI) quintiles, different regions and in China from the Global Burden of Disease (GBD) study 2019.ResultsGlobally, the death rate and DALYs due to ACM were 71 723 and 2 441 108 in 2019, 33.06% and 38.79% increase from 1990, respectively. The corresponding ASDR and age-standardized DALY rate decreased with EAPC of -1.52 (95% uncertainty interval (UI) = -2.39, -0.65) and -1.12 (95% UI = -2.14, -0.10). The high-middle SDI regions, especially Eastern Europe, showed the highest number of ACM-related deaths and DALYs. The ACM-related deaths and DALYs were 2545 and 87823 in China in 2019, 171.03% and 147.17% increase from 1990, respectively. Unlike the world level, ASDR and age-standardized DALY rate also increased in China. The ACM burden is higher in men, and people with 50 to 69 years old accounted for the most.ConclusionsACM burden in China and across the world increased substantially from 1990 to 2019. The greatest burden was borne by the high-middle SDI regions, especially by men aged 50-69 years old. Geographically and gender-age tailored strategies were needed to prevent ACM.

(-)-Carvone Modulates Intracellular Calcium Signaling with Antiarrhythmic Action in Rat Hearts.

ResumoFundamento:A (-)-carvona é um monoterpeno encontrado em óleos essenciais com atividade antioxidante e anti-inflamátoria.Objetivos:O objetivo deste estudo foi analisar a propriedade antiarrítmica da (-)-carvona no coração de rato e seus efeitos sobre a sinalização de Ca+2 intracelular.Métodos:Os efeitos da (-)-carvona foram avaliados sobre a contratilidade atrial (0,01 – 4 mM) e ventricular (0,5 mM), e no eletrocardiograma (0,5mM). A fração de encurtamento, a corrente de cálcio do tipo L (ICa,L) e a sinalização de Ca+2 foram medidas no cardiomiócito isolado (0,5 mM). O efeito antiarrítmico foi avaliado no modelo de arritmia induzida por sobrecarga de cálcio (0,5 mM) (n = 5). Um p < 0,05 foi adotado como nível de significância estatística.Resultados:No átrio, a (-)-carvona causou inotropismo negativo de maneira concentração-dependente (EC50 0,44 ± 0,11 mM) e diminuiu o inotropismo positivo induzido pelo CaCl2 (0,1 – 8,0 mM) e BAY K8644 (5 - 500 nM), um agonista de canal de cálcio do tipo L. Em coração isolado, a (-)-carvona (0,5mM) reduziu a contratilidade ventricular em 73% e a frequência cardíaca (em 46%), aumentou o Pri (30,7%, tempo desde o início da onda P até a onda R) e o QTc (9,2%, uma medida de despolarização e repolarização dos ventrículos), sem mudar a duração do complexo QRS. A (-)-carvona diminuiu a fração de encurtamento (61%), a (ICa,L) (79%) e o transiente intracelular de Ca+2 (38%). Além disso, a (-)-carvona apresentou ação antiarrítmica, identificada pela redução do escore de arritmia (85%) e ocorrência de fibrilação ventricular.Conclusão:A (-)-carvona reduz a entrada de Ca+2 através de canais de Ca+2 do tipo L e, assim, diminui a contratilidade cardíaca e o Ca+2 intracelular e apresenta promissora atividade antiarrítmica no coração de ratos.

Evaluation of left ventricular myocardial stratified strain in patients with Kawasaki disease using two-dimensional speckle tracking imaging.

Kawasaki disease (KD) is an acute autoimmune self-limited disease of unknown etiology. We aimed to evaluate the left ventricular myocardial stratified strains in children with KD in different stages using two-dimensional speckle tracking imaging, and to find the index that can early predict myocardial function injury in children with KD. A total of 73 children with KD were divided into acute, convalescent, and chronic stages according to the disease course. All children had no coronary artery damage. Further, 64 normal children were selected as the control group. The longitudinal and circumferential strain peaks of each myocardium were recorded, and the left ventricular global longitudinal strain (LVGLS), global circumferential strain (LVGCS), and transmural gradient between endocardium and epicardium (ΔGLS, ΔGCS) were calculated. Compared with the control group, LVGLS, GLS-Endo, GLS-Mid, GLS-Epi, and ΔGLS decreased in acute KD; LVGLS, GLS-Endo, GLS-Mid, GLS-Epi, ΔGLS, LVGCS, GCS-Mid, and GCS-Epi decreased in the convalescent stage; and only GLS-Endo was lower in children with chronic KD (P < 0.05). ROC curve was used to calculate the stratified strain parameters so as to predict left ventricular systolic function in children with acute KD; the area under the LVGLS curve was the largest (AUC = 0.953, P < 0.001). When the cutoff value of LVGLS was −19.89%, the sensitivity and specificity were 95.8% and 83.2%, respectively.ConclusionsThe systolic function of the whole layer of the myocardium decreased to varying degrees in children with KD. With the extension of the disease course, the myocardial function gradually recovered, but the subendocardial myocardium was still damaged. LVGLS could identify the abnormity of left ventricular contractility in patients with KD at the acute stage. Thus, it has the promising prospect of clinical diagnosis.

Ventricular-arterial decoupling is associated with in-hospital adverse events in normotensive pulmonary embolism.

During acute pulmonary embolism (PE) a compensatory increase in right ventricular (RV) contractility is required to match increased afterload to maintain right ventricular-pulmonary arterial (RV-PA) coupling. The aim of this study was to assess the prognostic utility of RV-PA decoupling in acute PE. We assessed the association between measures of transthoracic echocardiography (TTE)-derived RV-PA coupling including tricuspid annular plane systolic excursion (TAPSE)/right ventricular systolic pressure (RVSP) and right ventricular fractional area change (FAC)/RVSP as well as stroke volume index (SVI)/RVSP (a measure of pulmonary artery capacitance) with adverse PE-related events (in-hospital PE-related mortality or cardiopulmonary decompensation) using logistic regression analysis. In 820 normotensive patients TTE-derived markers of RV-PA coupling were associated with PE-related adverse events. For each 0.1mm/mmHg decrease in TAPSE/RVSP the odds of an adverse event increased by 2.5-fold [adjusted OR (aOR) 2.49, 95% confidence interval (CI) 1.46-4.24, p = 0.001], for every 0.1%/mmHg decrease in FAC/RVSP the odds of an adverse event increased by 1.4-fold (aOR 1.42, CI 1.09-1.86, p = 0.010), and for every 0.1mL/mmHgm2 decrease in SVI/RVSP the odds of an event increased by 2.75-fold (aOR 2.78, CI 1.72-4.50, p < 0.001). In multivariable analysis, TAPSE/RVSP and SVI/RVSP were independent of other risk stratification methods including computed tomography-derived right ventricular dysfunction (RVD), the Bova score, and subjective assessment of TTE-derived RVD. In patients with normotensive acute PE, TTE-derived measures of RV-PA coupling are associated with adverse in-hospital PE-related events and provide incremental value in the risk assessment beyond computed tomography-derived RVD, the Bova score, or subjective TTE-derived RVD.

Prevalence and factors associated with impaired left ventricular global longitudinal strain in patients with Chagas disease: SaMi-Trop cohort study.

Cardiomyopathy is a major cause of death in Chagas disease and early detection of cardiac involvement is essential. Myocardial strain is a reliable technique for assessment of subtle left ventricular (LV) contractility alterations. This study assessed LV global longitudinal strain (GLS) in a large Chagas disease population living in remote areas. Between 2015 and 2016, Chagas disease patients were selected in the northern of the Minas Gerais state. All patients underwent T. cruzi antibodies tests and those who had positive tests were included. A resting 12-lead ECG was recorded and classified using the Minnesota Code criteria. Echocardiography was performed at public health primary care units and speckle-tracking strain was analyzed offline. LV dysfunction was defined as ejection fraction (LVEF < 50%) and reduced GLS was defined as < 16% (absolute value). A total of 1387 patients were included, mean age of 60.0 ± 12.5years, 68% were women, and 14% had LV dysfunction. Among patients with normal LVEF, 59% had impaired LV GLS. Overall, patients with impaired GLS were older, had more comorbidities and ECG abnormalities than those with normal GLS. The independent factors associated with reduced GLS were ST-T abnormalities (OR 1.954; 95% CI 1.027-3.718), QRS duration (OR 1.009; 95% CI 1.002-1.016), LVEF (OR 0.947; 95% CI 0.923-0.972), and E/e' ratio (OR 1.059; 95% CI 1.009-1.112). In a cohort of Chagas disease from endemic areas, impaired LV GLS was detected in a significant proportion of patients, despite normal ECG and preserved LVEF. The main determinants of reduced LV GLS were ST-T abnormalities, QRS duration, LVEF and E/e' ratio, adjusting for demographical and clinical data.

Особливості зміни показників кумулятивного виживання пацієнтів з гострим коронарним синдромом без стійкої елевації сегмента ST, яким перкутанні коронарні втручання проводили в різні терміни від початку захворювання

Мета роботи – оцінити вплив реваскуляризації міокарда, яка була виконана хворим з гострим коронарним синдромом без стійкої елевації сегмента ST у різні терміни від початку симптомів, на ультразвукові показники скорочувальної функції лівого шлуночка та на функціональний клас стенокардії через 12 місяців спостереження. Матеріали і методи. Пацієнти з гострим інфарктом міокарда без стійкої елевації сегмента ST (NSTEMI), які увійшли в дослідження (n=128), були поділені на групи за часом проведення реваскуляризації (ургентна або планова реваскуляризація), а також за способом реваскуляризації (коронарне стентування або шунтування) на 5 груп, у тому числі групу хворих з NSTEMI, яким стентування не проводили. 1-шу групу (n=28) становили пацієнти, яким були виконані ургентні коронарографія та стентування ad hoc у перші 72 год від початку симптомів. У 2-гу групу (n=61) увійшли пацієнти, яким коронарографію і стентування проводили планово через 72 год і більше до кількох місяців від початку розвитку симптоматики. У 3-тю групу (n=12) увійшли пацієнти, яким у плановому порядку виконували коронарне шунтування. 4-та група (n=27) складалася з пацієнтів, яким після коронарографії реваскуляризацію не проводили («контрольна група»). 5-ту групу (n=101) склали пацієнти вищеозначених груп, яким була проведена будь-яка реваскуляризація. Результати та обговорення. Ефективність лікування і частота виникнення серйозних кардіоваскулярних подій у пацієнтів з NSTEMI статистично значуще залежить від наявності в стратегії лікування перкутанних і хірургічних методик реваскуляризації. Доповнення процедури реваскуляризації статистично значуще поліпшує прогноз, статистично значуще знижує комбінований показник МАСЕ (major adverse cardiac events, серйозні кардіоваскулярні події) у період спостереження за пацієнтами (до 48 міс) порівняно з групою контролю (p=0,000001). При прямому порівнянні групи ургентного коронарного стентування (протягом 72 год від початку симптомів) пацієнтів з NSTEMI з GRACE Score &gt;140 балів виявлено статистично значущу розбіжність за кількістю серйозних кардіоваскулярних подій за 48 міс спостереження (p&lt;0,05) порівняно з групою контролю GRACE Score &gt; 140.Висновки. Віддалені результати стентування пацієнтів з NSTEMI з високим ризиком ускладнень (група ургентного стентування) не мали переваг перед результатами лікування стабільних пацієнтів з NSTEMI (група планового стентування) після їх ефективної стабілізації на тлі оптимальної медикаментозної терапії. При порівнянні частоти МАСЕ у цих двох групах перевагу зі слабким ступенем статистичної значущості (p&lt;0,05) було виявлено в групі стабілізованих пацієнтів, що повністю підтверджує стратегію стратифікації хворих з нестабільним коронарним кровоплином на групи ризику ускладнень. Однак ургентні втручання абсолютно показані пацієнтам з високим ризиком ускладнень у перші дні від початку симптомів дестабілізації.

Relaxin does not prevent development of hypoxia-induced pulmonary edema in rats

Acute hypoxia impairs left ventricular (LV) inotropic function and induces development of pulmonary edema (PE). Enhanced and uneven hypoxic pulmonary vasoconstriction is an important pathogenic factor of hypoxic PE. We hypothesized that the potent vasodilator relaxin might reduce hypoxic pulmonary vasoconstriction and prevent PE formation. Furthermore, as relaxin has shown beneficial effects in acute heart failure, we expected that relaxin might also improve LV inotropic function in hypoxia. Forty-two rats were exposed over 24 h to normoxia or hypoxia (10% N2 in O2). They were infused with either 0.9% NaCl solution (normoxic/hypoxic controls) or relaxin at two doses (15 and 75 μg kg−1 day−1). After 24 h, hemodynamic measurements and bronchoalveolar lavage were performed. Lung tissue was obtained for histological and immunohistochemical analyses. Hypoxic control rats presented significant depression of LV systolic pressure by 19% and of left and right ventricular contractility by about 40%. Relaxin did not prevent the hypoxic decrease in LV inotropic function, but re-increased right ventricular contractility. Moreover, hypoxia induced moderate interstitial PE and inflammation in the lung. Contrasting to our hypothesis, relaxin did not prevent hypoxia-induced pulmonary edema and inflammation. In hypoxic control rats, PE was similarly distributed in the apical and basal lung lobes. In relaxin-treated rats, PE index was 35–40% higher in the apical than in the basal lobe, which is probably due to gravity effects. We suggest that relaxin induced exaggerated vasodilation, and hence pulmonary overperfusion. In conclusion, the results show that relaxin does not prevent but rather may aggravate PE formation.

L-Carnitine therapy improves right heart dysfunction throughCpt1-dependent fatty acid oxidation.

Pulmonary arterial hypertension (PAH) is a fatal vasculopathy that ultimately leads to elevated pulmonary pressure and death by right ventricular (RV) failure, which occurs in part due to decreased fatty acid oxidation and cytotoxic lipid accumulation. In this study, we tested the hypothesis that decreased fatty acid oxidation and increased lipid accumulation in the failing RV is driven, in part, by a relative carnitine deficiency. We then tested whether supplementation of l‐carnitine can reverse lipotoxic RV failure through augmentation of fatty acid oxidation. In vivo in transgenic mice harboring a human BMPR2 mutation, l‐carnitine supplementation reversed RV failure by increasing RV cardiac output, improving RV ejection fraction, and decreasing RV lipid accumulation through increased PPARγ expression and augmented fatty acid oxidation of long chain fatty acids. These findings were confirmed in a second model of pulmonary artery banding‐induced RV dysfunction. In vitro, l‐carnitine supplementation selectively increased fatty acid oxidation in mitochondria and decreased lipid accumulation through a Cpt1‐dependent pathway. l‐Carnitine supplementation improves right ventricular contractility in the stressed RV through augmentation of fatty acid oxidation and decreases lipid accumulation. Correction of carnitine deficiency through l‐carnitine supplementation in PAH may reverse RV failure.

The value of preservation of subvalvular structures in patients with mitral and aortic valve replacement surgery and its effect on left ventricular contractility

Objective: To discuss the clinical value of preserving subvalvular structure in mitral and aortic valve replacement surgery and its effect on left ventricular contractility. Methods: A total of 97 patients who underwent mitral valve replacement surgery in the Adult Cardiac Surgery of Heart Center of Henan Provincial People's Hospital, Central China Fuwai Hospital from June 2016 to December 2018 were selected as the research subjects, of whom 45 cases were preserved subvalvular structure and 52 cases were in the total resection group (intraoperative total resection of the mitral valve and subvalvular chordae tendineae). General cardiac function indexes and left ventricular function quantitative indexes were compared before and in 3 months and 6 months after the operation of the two groups; The changes of the overall longitudinal strain of the long axis of the apex and the overall circumferential strain of the short axis of the left ventricle determined by the two-dimensional speckle tracking technology were compared before and after the operation. Results: The ages of the patients in the preservation group and the total resection group were (41.8±11.3) and (43.3±10.6) years old, respectively, and the male proportions were 58.0% (26 cases) and 44.0% (23 cases), respectively, with no significant difference (all P>0.05). The aortic occlusion time and cardiopulmonary bypass time of the patients in the preservation group were (57.8±4.5) and (78.6±6.7) min, respectively, which were longer than those in the total resection group [(48.1±4.4) and (48.1±4.4) min, respectively] (all P<0.05). The left atrial pressure of the patients in the preservation group at shutdown was (8.4±1.8) mmHg (1 mmHg=0.133 kPa), which was lower than that of the total resection group (11.3±2.5) mmHg (P<0.001). There were interaction effects between groups and time in regards to the left ventricular end-diastolic diameter ( LVEDD ), left ventricular ejection fraction ( LVEF ) and Tei index, as well as the strain rate of mitral annulus and left ventricular wall of interventricular septum of the preservation group and the total resection group (all P<0.05). LVEDD and LVEF of patients in the preservation group at 3rd month after operation were (44.7±4.0) mm and (45.5±4.2) mm, and at 6th months were (56.5±4.9)% and (58.8±5.0)%, respectively, all larger than (42.7±3.6) mm and (42.7±3.6) mm, (54.5±4.6)% and (56.3±4.8)% of the total resection group. The measured value of LVESD in the preservation group at 3rd month after surgery was (32.6±3.2) mm, which was greater than that in the total resection group (31.2±3.4) mm (P<0.05). The Tei index of patients in the preservation group at 3rd and 6th months after surgery were 1.0±0.2 and 0.8±0.2, respectively, which were lower than those in the total resection group 1.2±0.3 and 0.9±0.2 (all P<0.05). Conclusion: Preserving the subvalvular structure during mitral valve replacement surgery can better improve the patient's left ventricular function and left ventricular systolic capacity.

Alterations in right ventricular mechanics in patients with Behcet's disease.

Manifest myocardial involvement is somewhat rare in patients with Behcet's disease (BD), although echocardiographic studies suggest that subclinical alterations in left ventricular (LV) contractility is rather common. Data on right ventricular (RV) involvement in BD is rather scarce.This study aims to determine whether RV systolic performance is affected in BD patients, and to understand the clinical and echocardiographic correlates of RV contractility in these patients.Forty-five patients who fulfilled criteria for BD and 45 age and gender matched controls were enrolled. All participants underwent a comprehensive echocardiographic examination, including deformation imaging, to characterize RV mechanics.Conventional morphologic and echocardiographic indicators of RV morphology and function were not different between groups, but RV apical strain and RV free wall strain (FWS) were significantly lower in BD patients as compared to the controls (P < 0.001 and P = 0.02, respectively). The only significant correlates of FWS were tricuspid regurgitation velocity and related indices in healthy controls, while FWS correlated with LV global longitudinal strain (GLS), morphologic measures of left and right atria and ventricles, and with conventional measures of right ventricular contractility. The relationship between FWS and GLS remained statistically significant after adjusting for other clinical and echocardiographic parameters (β = 0.379, P = 0.01).In patients with BD, there is a subclinical alteration in RV contractility and the degree of alteration in the RV systolic performance paralleled that of LV. Thus, present results support the presence of RV involvement in these patients.