Reduction In Left Ventricular Function Research Articles

Left ventricular systolic function in patients with acute coronary syndrome-risk profile

Abstract Funding Acknowledgements None. Introductions and objectives Left ventricular (LV) systolic dysfunction is one of the most important determinants of long-term outcome in acute coronary syndrome (ACS). Aim To determine the impact of the patient’s risk profile on the LV systolic function. Methods A single-center cross-sectional cohort study that included 3093 patients with ACS without pre-existing LV dysfunction. The comparison was performed between patients who did or did not develop a reduction in LV systolic function during the index event (<50%/≥50%), analyzing patients’ demographic, clinical, biochemical data, LV functional data, and anatomical distribution of the coronary artery disease (CAD). Result 1369 patients out of 3093 developed LV systolic dysfunction (44.3%). They were predominantly males 75.1% (1028), p=0.002; older (63.39±11.04 vs 61.21±11.12, p<0.00000); had higher level of cardiac troponin (p=0.00002), higher stress glycemia (9.2±5.3; p=0.0000001), HbA1c (6.9±1.8, p=0.000003), WBC (11.7±4.1, p=0.00001), blood urea nitrogen (BUN) (6.8±3.7, p=0.000003), and creatinine (93.2±45.1 p=0.000167), and had anemia (OR 0.35 (CI 0.29–41, p=0.000012). They had more severe CAD (SINTAX score 16.8±8.4 p=0.000012). Patients with preserved LV systolic function were predominantly females (29.7%, OR 1.1 95% CI 1.0-1.2), p = 0.002), younger (p<0.00000), and severely metabolically burdened (hypothyreosis (2.7%, OR 1.28 95% CI 0.93-1.76, p=0.052), higher levels of triglycerides (2.2±1.7 vs 1.9±1.5, p = 0.001), cholesterol (5.3±1.4 vs 5.2±1.4, p = 0.002), non-HDL-C (4.1±1.5 vs 3.9±1.3, p=0.006), however less likely to have pre-existing DM (OR 0.8 (CI 0.78–0.92), p=0.000094). They were more often NSTEMI [851 (49.4%), p = 0.000012]. Independent variables associated with a reduction in LV function were: advanced age, male gender, previous DM and anemia, stress glycemia, WBC, creatinine, and BUN. Conclusion Patients who developed reduced LV function had a very specific risk profile with bigger neuro-hormonal activation and inflammation, higher degree of myocardial damage, and worse renal function, whereas those with preserved LV systolic function after ACS were younger, predominantly females, more severely metabolically burdened, more often with NSTEMI and without LAD involvement.

The clinically active PARP inhibitor olaparib ameliorates doxorubicin-induced cardiotoxicity in both in vitro and in vivo model

Abstract Introduction Inhibition of poly (ADP-ribose) polymerase (PARP) has been shown to be cardioprotective in acute and chronic myocardial injury. Additionally, PARP inhibitor, Olaparib, is a clinically effective anti-cancer agent. Activation of PARP pathway has been suggested to be involved in cardiotoxicity arising from Doxorubicin (DOX, one of the most used anticancer drugs). It is thus, entirely possible that PARP inhibition could be a novel pathway to prevent DOX-induced cardiotoxicity (DIC). Purpose To determine the cardioprotective effects of Olaparib in preventing DOX-induced cardiotoxicity in in vitro and in vivo models. Methods In vitro: Human cardiomyocytes (HCMs) were treated with DOX at 1uM (EC50) +/- various doses (15.6nM, 1uM, 80uM, 100uM and 150uM) of Olaparib at 72hrs. Cell viability was assessed via CellTiter-Glo®. The mRNA expressions of treated HCMs were performed by qPCR. In vivo: Female C57BL/6 mice (6-8 weeks old) were administered: A) DOX at 5mg/kg/week for 6 weeks via IP injections, B) vehicle of 0.9% saline and 5% DMSO in PBS, C) Olaparib at 50mg/kg was administered 3 times/week, D) Olaparib at 50mg/kg was administered 3 times/week, followed by DOX treatments. Cardiac function was assessed by echocardiography at baseline and end of 6 weeks’ treatment. Results For the in vitro model, Doxorubicin induced marked reduction in HCMs cell viability. Concomitant Olaparib treatment at higher doses (80uM, 100uM, 150uM) significantly preserved DOX-induced cell viability after 72 hours of treatment. Molecular analysis in HCMs showed DOX-induced upregulation of mRNA gene expressions for apoptosis: Casp3, DNA damage: BBC3, and cardiac remodelling: TGF-β; all of which were reversed by Olaparib. In vivo: we found significant reduction of left ventricular function and increased ventricular wall thickness in DOX treated group after 6 weeks’ treatment compare to baseline [LVEF%: 52.4±1.3 vs.56.5±2.0, P=0.02; FS%:16.7±1.4 vs. 20.1±1.3, P=0.03; Total Wall thickness (mm):2.1±0.1 vs. 1.9±0.1, P<0.05]; whereas the mice pre-treated with Olaparib in combination with DOX showed preservation of cardiac functions between endpoint and baseline. Conclusion Olaparib protected HCMs against DIC and improved cardiac function in DIC mice model. Our findings indicate that Olaparib could provide cardioprotection in DOX-induced cardiotoxicity.

Endothelial MICU1 alleviates diabetic cardiomyopathy by attenuating nitrative stress-mediated cardiac microvascular injury

BackgroundMyocardial microvascular injury is the key event in early diabetic heart disease. The injury of myocardial microvascular endothelial cells (CMECs) is the main cause and trigger of myocardial microvascular disease. Mitochondrial calcium homeostasis plays an important role in maintaining the normal function, survival and death of endothelial cells. Considering that mitochondrial calcium uptake 1 (MICU1) is a key molecule in mitochondrial calcium regulation, this study aimed to investigate the role of MICU1 in CMECs and explore its underlying mechanisms.MethodsTo examine the role of endothelial MICU1 in diabetic cardiomyopathy (DCM), we used endothelial-specific MICU1ecKO mice to establish a diabetic mouse model and evaluate the cardiac function. In addition, MICU1 overexpression was conducted by injecting adeno-associated virus 9 carrying MICU1 (AAV9-MICU1). Transcriptome sequencing technology was used to explore underlying molecular mechanisms.ResultsHere, we found that MICU1 expression is decreased in CMECs of diabetic mice. Moreover, we demonstrated that endothelial cell MICU1 knockout exacerbated the levels of cardiac hypertrophy and interstitial myocardial fibrosis and led to a further reduction in left ventricular function in diabetic mice. Notably, we found that AAV9-MICU1 specifically upregulated the expression of MICU1 in CMECs of diabetic mice, which inhibited nitrification stress, inflammatory reaction, and apoptosis of the CMECs, ameliorated myocardial hypertrophy and fibrosis, and promoted cardiac function. Further mechanistic analysis suggested that MICU1 deficiency result in excessive mitochondrial calcium uptake and homeostasis imbalance which caused nitrification stress-induced endothelial damage and inflammation that disrupted myocardial microvascular endothelial barrier function and ultimately promoted DCM progression.ConclusionsOur findings demonstrate that MICU1 expression was downregulated in the CMECs of diabetic mice. Overexpression of endothelial MICU1 reduced nitrification stress induced apoptosis and inflammation by inhibiting mitochondrial calcium uptake, which improved myocardial microvascular function and inhibited DCM progression. Our findings suggest that endothelial MICU1 is a molecular intervention target for the potential treatment of DCM.

Phenotypic variability of filamin C–related cardiomyopathy: Insights from a novel Dutch founder variant

Dilated cardiomyopathy (DCM) can be caused by truncating variants in the filamin C gene (FLNC). A new pathogenic FLNC variant, c.6864_6867dup, p.(Val2290Argfs*23), was recently identified in Dutch DCM patients. The report aimed to evaluate the phenotype of FLNC variant carriers and to determine whether this variant is a founder variant. Clinical and genetic data were retrospectively collected from variant carriers. Cardiovascular magnetic resonance (CMR) studies were reassessed. Haplotypes were reconstructed to determine a founder effect. The geographical distribution and age of the variant were determined. Thirty-three individuals (70% female) from nine families were identified. Sudden cardiac death was the first presentation in a carrier at 28 years of age. Median age at diagnosis was 41 years (range 19-67). The phenotype was heterogeneous. DCM with left ventricular (LV) dilation and reduced ejection fraction (<45%) was present in eleven individuals (33%), three (9%) of whom underwent heart transplantation. CMR showed late gadolinium enhancement (LGE) in 65% of the assessed individuals, primarily in a ring-like distribution. Non-sustained ventricular arrhythmias were detected in six (18%), and five (15%) individuals received an implantable cardioverter defibrillator. A shared haplotype spanning 2.1 Mb was found in all haplotyped individuals. The variant originated between 275-650 years ago. The pathogenic FLNC variant c.6864_6867dup, p.(Val2290Argfs*23) is a founder variant originating from the south of the Netherlands. Carriers are susceptible to developing heart failure and ventricular arrhythmias. The cardiac phenotype is characterized by ring-like LGE, even in individuals without significantly reduced LV function.

Characterizing the hypertensive cardiovascular phenotype in the UK Biobank.

To describe hypertension-related cardiovascular magnetic resonance (CMR) phenotypes in the UK Biobank considering variations across patient populations. We studied 39 095 (51.5% women, mean age: 63.9 ± 7.7 years, 38.6% hypertensive) participants with CMR data available. Hypertension status was ascertained through health record linkage. Associations between hypertension and CMR metrics were estimated using multivariable linear regression adjusting for major vascular risk factors. Stratified analyses were performed by sex, ethnicity, time since hypertension diagnosis, and blood pressure (BP) control. Results are standardized beta coefficients, 95% confidence intervals, and P-values corrected for multiple testing. Hypertension was associated with concentric left ventricular (LV) hypertrophy (increased LV mass, wall thickness, concentricity index), poorer LV function (lower global function index, worse global longitudinal strain), larger left atrial (LA) volumes, lower LA ejection fraction, and lower aortic distensibility. Hypertension was linked to significantly lower myocardial native T1 and increased LV ejection fraction. Women had greater hypertension-related reduction in aortic compliance than men. The degree of hypertension-related LV hypertrophy was greatest in Black ethnicities. Increasing time since diagnosis of hypertension was linked to adverse remodelling. Hypertension-related remodelling was substantially attenuated in hypertensives with good BP control. Hypertension was associated with concentric LV hypertrophy, reduced LV function, dilated poorer functioning LA, and reduced aortic compliance. Whilst the overall pattern of remodelling was consistent across populations, women had greater hypertension-related reduction in aortic compliance and Black ethnicities showed the greatest LV mass increase. Importantly, adverse cardiovascular remodelling was markedly attenuated in hypertensives with good BP control.

P348 COMBINATION THERAPY IN A PATIENT WITH TTRV AMYLOIDOSIS

Abstract 73 year old male. He has a brother with an unspecified heart disease, three children, all in good health. Former smoker, arterial hypertension, bilateral carpal tunnel syndrome for several years. Therapy used: zofenopril 7.5 mg 1 cp/day. In August 2019 hospitalization for acute heart failure. Echocardiogram showed severe concentric left ventricular hypertrophy with a granular sparkling myocardial appearance, moderately reduced EF, moderate mitral regurgitation, restrictive transmitral pattern, and pulmonary hypertension (PAPS 60 mmHg). ICV with increased dimensions and not collapsible. Moderate circum–cardiac pericardial effusion. During this hospitalization, therapy with an ACE inhibitor, beta blocker and MRI was started with clear clinical benefit. He also started anticoagulant therapy for evidence of atrial fibrillation. At discharge, NYHA class II. Myocardial scintigraphy with bone tracer was positive for the presence of grade 2 myocardial uptake according to the Perugini score. Blood chemistry tests were performed to exclude the AL form and finally the genetic test showed the presence of a mutation on the transthyretin Val122Ile gene (mutation associated with a variant of amyloidosis with a predominantly cardiological phenotype). Then, heart failure therapy was optimized and disease modifying therapy was started with Tafamidis 61 mg/day. Over time there was a reduction in left ventricular function, so sacubitril/valsartan was started; this drug was not tolerated due to hypotensive episodes. The NYHA class has however always remained stable (class II). During the follow–up in September 2022 he had a new hospitalization for heart failure during which the therapy was optimized with the insertion of the SGLT–2 inhibitor, which was well tolerated. During this hospitalization, symptoms related to the neurological involvement of the pathology emerged: severe weight loss and paresthesias in the four limbs for which it was decided to associate therapy with patisiran IV. To date, the approved therapy for amyloid cardiomyopathy is tafamidis but, in consideration of the neurological symptoms and the results obtained from patisiran in patients with the variant form, it was decided to associate the two therapies, taking care to also optimize therapy for heart failure.

Survival of Myocardial Infarction Patients with Diabetes Mellitus at the Invasive Era (Results from the Városmajor Myocardial Infarction Registry).

Due to the lifelong nature of diabetes mellitus (DM), it has been demonstrated to have significant effects on patients' morbidity and mortality. The present study aimed to assess the effects of DM on the clinical outcome and survival in patients who underwent percutaneous coronary intervention (PCI) due to myocardial infarction (MI) and to examine the relationship of DM to the type of the MI and to left ventricular (LV) and renal functions. A total of 12,270 patients with ST-elevation MI (STEMI) or non-ST-elevation MI (NSTEMI) were revascularized at our Institution between 2005 and 2013. In this pool of patients, 4388 subjects had DM, while 7018 cases had no DM. In both STEMI and NSTEMI, the 30-day and 1-year survival were worse in diabetic patients as compared to non-diabetic cases. In the patients with DM, NSTEMI showed worse prognosis within 1-year than STEMI similarly to non-diabetic subjects. Regarding survival, the presence of DM seemed to be more important than the type of MI. Regardless of the presence of DM, reduced LV function was a maleficent prognostic sign and DM significantly reduced the prognosis both in case of reduced and normal LV function. Survival is primarily affected by LV function, rather than DM. Worse renal function is associated with worse 30-day and 1-year survival in both cases with and without DM. Considering different renal functions, the presence of DM worsens both short- and long-term survival. Survival is primarily affected by renal function, rather than DM. The results from a high-volume PCI center confirm significant the negative prognostic impact of DM on survival in MI patients. DM is a more important prognostic factor than the type of the MI. However, survival is primarily affected by LV and renal functions, rather than DM. These results could highlight our attention on the importance of recent DM treatment with new drugs including SGLT-2 inhibitors and GLP-1 antagonists with beneficial effects on survival.

Incidence and Types of Arrhythmias in Acute Coronary Syndrome: An Observational Study

their diagnosis is not considered in contemporary acute coronary syndrome patients. This study investigates the incidence and types of arrhythsmias among acute coronary syndrome patients presenting to the emergency department, as well as their association with various factors and patient outcomes. Methods: The current prospective observational study was conducted at a tertiary care center in Kolkata, India. Data were collected from 76 acute coronary syndrome patients admitted between October 2020 and May 2021 to the emergency department. Information was gathered through semi-structured interviews and relevant investigations. Results: The majority of the patients were aged 61-70 years, with three fourth of the study population being male. The incidence of arrhythmia was diagnosed in 77.6% of the patients. The most common arrhythmias were sinus tachycardia, ventricular premature complex, atrial fibrillation, sinus bradycardia, and complete heart block. Arrhythmias were more prevalent among ST-elevation myocardial infarction (62.7%) and unstable angina (8.5%) patients. Patients with Left Ventricular Ejection Fraction ≤ 40% had a higher incidence of arrhythmias (93.5%). The mortality rate during hospital stay was 11.9% among acute coronary syndrome patients with arrhythmias, while all acute coronary syndrome patients without arrhythmia had a 100% survival rate. Conclusion: This study highlights the incidence and types of arrhythmias in acute coronary syndrome patients presenting to the emergency department. It reveals a higher prevalence of arrhythmias in specific subgroups, such as patients with ST-elevation myocardial infarction and those with a reduction in left ventricular function. These findings contribute to our understanding of arrhythmias in acute coronary syndrome and their association with patient outcomes, emphasizing the importance of appropriate management and monitoring in this population.

1009 INTRAMYOCARDIAL HEMORRHAGE: A DIFFERENTIAL DIAGNOSIS OF HYPERTROPHY

Abstract Hypertrophic cardiomyopathy (HCM) is a muscle disorder with impairment of microvascular circulation. Intramyocardial hemorrhage (IMH) represents a possible complication in patients with myocardial infarction (MI) involving left ventricular (LV) myocardial tissue and micro vascularization. We describe a case of a HCM patient with anterior STEMI with evidence of IMH. Case Report A 61-years-old male patient from Sri Lanka with no prior medical history presented to the emergency Department with persistent chest pain started from 3 hours. He was a smoker. The first ECG revealed ST-segment elevation in V2-5 leads and symmetric negative T-wave in I and aVL leads. Primary percutaneous coronary intervention (PCI) was performed, revealing sub-obstructive stenosis in the proximal left anterior descending artery (LAD) associated with extensive endoluminal thrombus. Invasive coronary angiogram also showed a critical stenosis in distal right coronary artery (RCA) and a chronic occlusion in the proximal left circumflex coronary artery (LCx). After tirofiban intravenous administration and rheolytic thromboaspiration, drug-eluting stent (DES) implantation of the LAD artery was performed successfully. Transthoracic echocardiography, performed after primary PCI, documented akinesia of proximal LAD territories and LV ejection fraction (EF) of 45%. The curious feature was the evidence of concentric hypertrophy in absence of an apparent reason. Therefore, three days later, the patient underwent cardiac magnetic resonance (CMR), showing mildly reduced LV function (LVEF 42%). CMR images also showed subendocardial late enhancement in proximal LAD territory and transmural LGE with no-reflow phenomenon in mid-apical anteroseptum. (Figure) On T2-weighted images, there was an hypointense core enclosed in the transmural hyperintense area in basal-mid anteroseptum, likely in keeping with intramyocardial hemorrhage (Figure). After a staged PCI with the implant of another DES in RCA, patient was discharged in DAPT (aspirin + ticagrelor). Conclusion IMH is considered a severe form of MVO, which occurs in the core of the infarcted area in patients with myocardial infarction. We describe an intriguing case with IHM in HCM patient. Moreover, it raises several questions on which is the best treatment option.

Abstract 14873: Analysis of Heart Failure Re-Admissions and In-Hospital Outcomes in Patients With Takotsubo Syndrome

Background: Takotsubo Syndrome (TTS) is characterized by transient reduction in left ventricular function with in the absence of obstructive coronary artery disease. Clinical presentation often mimics acute myocardial infarction (AMI). Patients with TTS have comparable long-term mortality with AMI patients. However, data on the burden of heart failure (HF) readmissions in patients with TTS are scarce. Methods: This retrospective analysis utilized the US Nationwide Readmission Database for the years 2012-2019 to identify hospitalizations for TTS or AMI. The primary outcome of interest was 6-month readmission due to HF. Secondary outcomes included in-hospital mortality. Results: There were 30,926 hospitalizations with TTS and 2,535,025 hospitalizations with AMI. The proportion of women was 90% among TTS patients and 37.7% among AMI patients (p&lt;0.001). Overall comorbidities were similar between the two groups, but in-hospital mortality during index admission was higher in the AMI arm (6.5% vs 1.5% in TTS, p &lt;0.01) accompanied with increased in-hospital complications. All-cause readmission rates were lower among TTS than among AMI patients (21.9% vs. 29.4%; p &lt;0.01). HF readmissions were also lower among TTS than AMI patients (3.7% vs. 6.7%; p &lt;0.01). After propensity matching, all-cause readmission rate remained lower among TTS than among AMI patients (21.9% vs. 27.9%; p &lt;0.01). HF hospital readmissions rates were also lower among TTS patients (3.7% vs 5.7%; p &lt;0.01). Independent predictors of HF readmission in TTS population included comorbidities such as diabetes mellitus, atrial fibrillation, chronic kidney disease, peripheral vascular disease, and chronic pulmonary disease. Conclusion A substantial proportion of patients (&gt;20%) with TTS suffer a hospital readmission within 6 months, although less than 5% are readmitted with HF. Compared with AMI, all-cause and HF readmission rates are lower in TTS patients.

Abstract 14461: Post Transcatheter Aortic Valve Replacement (TAVR) Mortality Outcomes in Patients With and Without Severe LV Dysfunction (LVEF&lt;35%): A Pooled Analysis

Background: Transcatheter aortic valve replacement (TAVR) is indicated in patients with severely reduced left ventricular ejection fraction (LVEF) and can restore left ventricular (LV) function. However, mortality outcomes in this unique subset of patients has been studied only in limited cohorts. Methods: Extensive search on PubMed and Google Scholar yielded 1069 reports meeting inclusion criteria. These studies were independently evaluated by 2 physicians. Nine studies comparing all-cause mortality in patients undergoing TAVR with and without severely reduced LVEF (&lt;35%) were included with a total of 31,952 patients. A study-level analysis was done using Review manager 5.3. As a guide, an I2 &gt;30% was considered an indicator of statistical heterogeneity among the studies. A Mantel-Haenszel Random effects model was used to calculate the Odds Ratio for homogeneous endpoints. A p value &lt;0.05 was considered significant. Results: 30-day and 1-year all-cause mortality was significantly higher among patients with severely reduced LVEF yielding Odds Ratios of 1.80[CI 1.33-2.87; p=0.01; I 2 = 77%] (A) and 1.81 [1.65-1.99 p&lt;0.001; I 2 = 26%] (B). respectively. Conclusion: There is a staggering 80% increased risk of short- and long-term mortality in patients with severely reduced LV function following TAVR. These findings are concerning despite lack of randomized data. Interdisciplinary management with advanced heart failure teams should be undertaken pre-emptively in these patients for close monitoring and early intervention.

Peripartum Cardiomyopathy

Peripartum cardiomyopathy (PPCM) is a rare but potentially life-threatening heart disease, with onset in the last month of pregnancy or in the first months after delivery in previously heart-healthy women. PPCM patients typically present with heart failure due to left ventricular (LV) dysfunction with an LV ejection fraction (EF) < 45 %. In the last years clinical and experimental studies contributed to a better understanding of the pathophysiology and the clinical course of PPCM. In the context of oxidative stress, the nursing hormone prolactin is cleaved into a smaller antiangiogenic and proapoptotic 16k Da form, leading to myocardial dysfunction. In an animal model this can be prevented by treatment with the dopamine agonist bromocriptine, which suppresses prolactin release. This therapeutic approach was confirmed in several clinical studies. Therefore, the current guidelines recommend a treatment consisting of a heart failure treatment according to current guidelines in combination with the dopamine agonist bromocriptine. If the diagnosis is made early and the treatment is started immediately, the prognosis is good compared to other forms of cardiomyopathies, as LV function recovers in most cases.In the acute phase the severity of heart failure differs among PPCM patients. Some patients present with mild forms, whereas some PPCM patients display severely reduced LV function and cardiogenic shock. Especially the latter cases are still challenging, as treatment with β1-adrenergic receptor agonists is associated with progression of heart failure and a worse cardiac outcome. Therefore, patients with cardiogenic shock complicating PPCM should be treated in centers experienced in mechanical circulatory support in combination with bromocriptine treatment.

The impact of complete versus partial preservation of the sub-valvular apparatus on left ventricular function in mitral valve replacement.

In mitral valve replacement (MVR), sudden increases in afterload and disruption of the annular-chordal-papillary-left-ventricular wall causes left ventricular(LV) dysfunction in the early postoperative period. Preservation of the posterior mitral leaflet apparatus (MVR-P) has a favorable outcome on LV function. However, there is paucity of data on the impact of complete preservation of the sub-valvular apparatus (MVR-C). We investigated the impact of MVR-P and MVR-C on baseline and 3-months postoperative LV ejection fraction (EF) and global longitudinal strain (GLS). We retrospectively analyzed a cohort of 29 MVR-P and 19 MVR-C patients with complete echocardiography data at our unit, who were operated between 2008 and 2017. Between-group changes in LVEF and GLS were compared using independent sample T-test. Median age was 59 years (IQR 50-69 years). Baseline LVEF was 58% (51%- 60%). Baseline GLS was -18.4 (-21.2 to -15.5). There were no significant between-group differences between all baseline demographics and echocardiographic markers. There was significantly higher absolute postoperative LVEF in MVR-C patients (p = 0.029). There was also significant worsening in LVEF (p = 0.0121) and GLS (p < 0.0001) after MVR-P and not MVR-C, suggesting no reduction in LV function post-MVR-C but a reduction post-MVR-P. There was significantly less postoperative worsening of GLS per patient in MVR-C group as compared to the MVR-P group (p = 0.023), indicating better preservation of LV function. There was also a smaller decline in LVEF per patient in the MVR-C as compared to the MVR-P group, although not statistically significant (p = 0.23). MVR with complete preservation of the sub-valvular apparatus shows a favorable impact on the longitudinal function of the heart at 3 months. Further studies with larger patient numbers are indicated to investigate the long-term results of this surgical approach.

Inefficient diastolic filling in dual-chamber pacemaker recipients: impact of atrio-ventricular interval shortening (AVI-SHORT study).

Adequate synchronization between the passive ("E") and active ("a") left ventricular (LV) diastolic filling contributes to the efficiency of the heartbeat. E/a superposition in dual-chamber pacemaker (PM) recipients is an under-recognized phenomenon that may be corrected by shortening the atrio-ventricular interval (AVI). We aimed at establishing the prevalence of E/a superposition in PM patients and to analyze the clinical, echocardiographic, and biological impact of AVI shortening. Seventy patients with dual-chamber PMs (74 ± 8years old, 12 women) were consecutively enrolled in this study. Patients with baseline E/a superposition were crossed over from default to manually shortened AVI or vice versa in a case-control fashion (intervention group). Patients without baseline E/a superposition (controls) served as a reference for a descriptive comparison with the intervention group. Thirty-three patients had E/a superposition after PM implantation (47%). Controls (n = 37) had higher LV ejection fraction (59 ± 8% vs. 53 ± 10%, p = 0.048) and lower levels of high sensitive troponin T and ST2 (p < 0.05) than intervention group patients. The AVI was shortened at 48 ± 9ms in order to ensure adequate E/a separation. The walked distance increased from 75 ± 17 to 78 ± 10% (p = 0.049) and the Euro-QoL score from 0.50 ± 0.27 to 0.63 ± 0.19 (p = 0.011) with short AVI. E/a superposition occurs in approximately half of dual-chamber PM recipients and is associated with reduced LV function and increased myocardial injury biomarkers. AVI shortening produces a modest but significant effect in functional capacity and quality of life.

Acute impact of transcatheter edge-to-edge repair for mitral regurgitation on left ventricular function

Abstract Introduction Transcatheter Edge-to-Edge repair (TEER) for the therapy of mitral valve regurgitation (MR) is an alternative to surgery for high risk patients. It is a minimal invasive procedure but the acute impact of the pre- and afterload decrease, due to the reduction of both MR and mitral valve area (MVA), on the left ventricle (LV) systolic function was never formally evaluated. Method Fifty patients with mixed MR etiologies from our TEER register with complete 3D datasets of the LV before and after TEER were included in this study. LV volumes and function, as evaluate by ejection fraction (LVEF), global longitudinal strain (LV-GLS) and global circumferential strain (LV-GCS), and the MR (3D vena contracta area, 3D VCA) were evaluated before and at the end of the therapy. Results The majority of patients suffered from secondary MR (54%), one TEER device was implanted in 64% and two in 36% of the population. TEER leads to a significant reduction of all the LV volume and function parameters excepted for the end-diastolic volume which increased non-significantly (Table 1). The decrease of the LVEF was linked to a decrease of both GLS and GCS in a multivariate analysis (r 0.85), the decrease of GCS having a higher influence (beta −0.606 vs −0.435). In the univariate linear analysis, the reduction of LVEF, GLS and GCS were inverse proportional to the LVEF before TEER and direct proportional to the reduction of the 3D VCA. LVEF decrease was also directly linked to MVA percental reduction. After multivariate evaluation, LVEF reduction kept linked to LVEF before TEER and VCA 3D reduction (r=0.51, p=0.001), GCS decrease only to VCA 3D reduction (r=0.371, P=0.08) and GLS diminution only to LVEF before TEER (r=0.313, p=0.027). Conclusion After TEER, left ventricular function reduction seems principally linked to the afterload increase (i.e. the MR reduction); the circumferential function and the left ventricles with the highest ejection fractions being apparently maximally impacted. Funding Acknowledgement Type of funding sources: None.

Midgestation cardiovascular phenotype in women who develop gestational diabetes and hypertensive disorders of pregnancy: comparative study.

Women with gestational diabetes mellitus (GDM) and/or hypertensive disorders of pregnancy (HDP) are at increased long-term cardiovascular risk. Mild cardiac functional alterations have been detected in women with GDM or HDP in midgestation, prior to clinical onset of the disease, but these functional alterations have not been found to be useful as screening tools. In contrast, increased impedance to peripheral blood flow, measured by echocardiography or ophthalmic artery Doppler, has been shown to provide incremental value to maternal characteristics for the prediction of pre-eclampsia. However, it is unknown whether similar changes can be detected in women at risk of GDM. In this study, we performed detailed cardiovascular phenotyping in a large, unselected population of women in midgestation to identify similarities and differences in cardiovascular adaptation in women who are at risk of GDM and/or HDP. This was a prospective observational study in women attending for a routine hospital visit at 19 + 1 to 23 + 3 weeks' gestation. This visit included assessment of flow velocity waveforms from the maternal ophthalmic arteries, echocardiography for assessment of maternal cardiovascular function and measurement of uterine artery pulsatility index and serum placental growth factor (PlGF) for assessment of placental perfusion and function. The measured indices were converted to either multiples of the median (MoM) values or deviation from the median (delta) after adjusting for maternal characteristics and elements of medical history. Biomarker delta or MoM values in the GDM and HDP groups were compared with those in the unaffected group using 95% CI and t-tests. The study population of 5214 pregnancies contained 4429 (84.9%) that were unaffected by GDM or HDP, 509 (9.8%) complicated by GDM without HDP, 41 (0.8%) with GDM and HDP, and 235 (4.5%) with HDP without GDM. In HDP cases, with or without GDM, there was evidence of impaired placentation, with a decrease in PlGF, and increased impedance to flow in the peripheral circulation, suggested by an increase in ophthalmic artery peak systolic velocity (PSV) ratio, peripheral vascular resistance assessed on echocardiography and mean arterial pressure. In the GDM group without HDP, there was no evidence of altered placental perfusion or function and ophthalmic artery PSV ratio was not significantly different from that in the unaffected group; peripheral vascular resistance and mean arterial pressure were increased but to a lesser degree than in the HDP group. In the HDP group, there was an increase in global longitudinal systolic strain and slight increase in isovolumic relaxation time, while in the GDM group, there was an increase in mitral valve E/e', myocardial performance index and global longitudinal systolic strain. In midgestation, women who subsequently develop HDP or GDM have a mild subclinical reduction in left ventricular function. In HDP cases, with or without GDM, there is evidence of impaired placentation and all biomarkers of impedance to peripheral blood flow are consistently increased. In contrast, in the GDM group without HDP, biomarkers of placental function are normal and those of impedance to peripheral blood flow are either marginally increased or not significantly different from those in normal pregnancies. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Survival and left ventricular dysfunction post lung transplantation for pulmonary arterial hypertension

PurposeBilateral lung transplantation for end-stage pulmonary arterial hypertension (PAH) is traditionally associated with higher early post-transplant mortality when compared with other indications. Changes in perioperative management, including the growing use of perioperative extracorporeal membrane oxygenation (ECMO) and an increased awareness of postoperative left ventricular dysfunction (LVD), have resulted in outcomes that are uncertain. Materials and methodsWe conducted a single-center, retrospective observational study at a lung transplantation center in Melbourne, Australia, from 2006 to 2019. ECMO use was categorized as preoperative, prophylactic, or rescue. Postoperative LVD was defined as a reduction in left ventricular function on echocardiography or using strict clinical criteria. Results50 patients underwent lung transplantation for PAH. 12-month survival was 48/50 (96%). ECMO was used in 26 (52%) patients, and the use of prophylactic VA-ECMO increased over the study period. Postoperative LVD was diagnosed in 21 (42%) patients. 12-month survival and left ventricular function was no different between LVD and non-LVD groups. ConclusionsThis study showed that high survival rates can be achieved following lung transplantation for PAH. We found that ECMO utilization was common, and indications have changed over time. LVD was common but did not impact 12-month survival.

The Prognostic Role of Mitral Valve Regurgitation Severity and Left Ventricle Function in Acute Heart Failure.

Aims: Data about the prognostic interplay between mitral regurgitation MR and left ventricular (LV) function in the outcome of patients admitted with acute heart failure (AHF) are scarce. We evaluated the prognostic impact of MR severity and LV function on mortality and on recurrent heart failure hospitalization (re-HFH) in patients admitted with AHF. Methods and Results: In total, 6843 patients admitted with AHF were evaluated: 2521 patients with LV ejection fraction (LVEF) ≤ 40% (reduced LVEF), 1238 of them (51%) having ≥moderate MR; and 4322 with LVEF > 40% (preserved LVEF), 1175 of them (27%) having ≥moderate MR. One-year mortality and re-HFH rates were higher in patients with ≥moderate MR unrelated to the baseline LV function (p = 0.028 and p < 0.001, respectively). After multivariable analysis, only reduced LVEF, and not the severity of MR, predicted mortality risk (HR: 1.31 [95% CI: 1.12–1.53] for patients with reduced LV function and ≤mild MR; HR: 1.44 [95% CI: 1.25–1.67] for patients with reduced LV function and ≥moderate MR); p < 0.001 for both. There was an increased risk for re-HFH in each group (HR: 1.35 [95% CI: 1.17–1.52] for patients with preserved LV function and ≥moderate MR; HR: 1.31 [95% CI: 1.15–1.51] for patients with reduced LV function and mild MR; and HR: 1.65 [95% CI: 1.45–1.88] for patients with reduced LV function and ≥moderate MR); p < 0.001 for all. Conclusions: In patients admitted with AHF, the LV function is the main prognostic determinant for mortality after 1 year. Significant (≥moderate) MR is associated with an increased risk of recurrent hospitalization.

Screening for Biomarkers Associated with Left Ventricular Function During Follow-up After Acute Coronary Syndrome

A proportion of patients with the acute coronary syndrome (ACS) will suffer progressive remodeling of the left ventricular (LV). The aim was to screen for important biomarkers from a large-scale protein profiling in 420 ACS patients and define biomarkers associated with reduced LV function early and 1 year after the ACS. Transferrin receptor protein 1 and NT-proBNP were associated with LV function early and after 1 year, whereas osteopontin and soluble ST2 were associated with LV function in the early phase and, tissue-type plasminogen activator after 1 year. Fatty-acid-binding protein and galectin 3 were related to worse GLS but not to LVEF 1 year after the ACS. Proteins involved in remodeling and iron transport in cardiomyocytes were related to worse LV function after ACS. Biomarkers for energy metabolism and fibrosis were exclusively related to worse LV function by GLS. Studies on the functions of these proteins might add knowledge to the biological processes involved in heart failure in long term after ACS.

Prevalence of left ventricular thrombus formation after mitral valve edge-to-edge repair

The prevalence of left ventricular (LV) thrombus formation following percutaneous mitral valve edge-to-edge repair (TMVR) with the MitraClip system is unclear. Decreased total stroke volume and perfusion of the LV apex after mitral valve repair may facilitate thrombus formation especially in the context of reduced LV function. LV thrombus may cause disabling stroke or other thromboembolic events in this elderly and multimorbid patient cohort. Analyses of the prevalence of and risk factors for left ventricular thrombus formation in patients treated with the MitraClip system due to severe mitral valve regurgitation. All discharge and follow-up transthoracic echocardiographic examinations up to 6 months of 453 consecutive patients treated with the MitraClip system were screened for the presence of LV thrombus. Prevalence of LV thrombus formation was 1.1% (5/453). Importantly, LV thrombi were exclusively found in patients with severely depressed left ventricular systolic function (LV-EF < 30%), comprising a prevalence of 4.4% in this subgroup (5/113). Importantly, two of these patients were under active DOAC therapy with Rivaroxaban and Apixaban, respectively. Apart from LV-EF, we did not identify other factors that might have facilitated LV thrombus formation. LV thrombus formation following percutaneous mitral valve repair occurred exclusively in patients with severely depressed LV-EF. As two patients developed LV thrombus despite of DOAC therapy, anticoagulation with a Vitamin K antagonist should be considered in patients with an indication for oral anticoagulation following TMVR.