Native Heart Research Articles

Prevalence of multiple native valvular heart disease in TAVR patients: a multicenter study assessing the impact of staged transcatheter edge-to-edge repair

Abstract Background Multiple valvular heart disease (VHD) is associated with poor prognosis in patients undergoing TAVR. Existing research focuses either on mitral or tricuspid regurgitation (MR, TR), without providing comparative analysis of their long-term effects. Moreover, whether staged transcatheter edge-to-edge repair (TEER) improves outcomes in these patients is unknown. Purpose This multicenter study aimed to evaluate the prevalence of multiple VHD within a recent TAVR cohort and to assess and compare the impact of concomitant severe MR and TR on outcomes at both one and five years post-TAVR. Additionally, we aimed to examine the potential impact of staged TEER for severe VHD in patients treated with TAVR. Methods The study cohort consisted of 2,823 patients undergoing TAVR at our Heart Center between 2015 and 2022. This representative cohort was used to investigate the prevalence of multiple VHD in a contemporary TAVR population and to assess and compare the impact of severe MR and TR on outcomes following TAVR. Additionally, this cohort, along with TAVR cohorts from other Heart Centers, was screened for additional valvular intervention. Patients who underwent staged transcatheter edge-to-edge repair for severe MR (n=147) or TR (n=59) were included. Results A concomitant persistent severe VHD was observed in 369 (13.1%) patients, with 208 (7.4%) having a severe MR, and 161 (5.7%) having a severe TR. The one-year mortality was significantly higher in patients with a severe VHD compared to the overall cohort (9.0 vs 5.2 per 100 PY, p<0.01). Notably, the highest one-year mortality was observed in patients with severe TR (13.3 per 100 PY) followed by patients with severe MR (6.4 per 100 PY) and those with no or a mild VHD (3.9 per 100 PY, p<0.01). This difference persisted over five years, with mortality rates of 27.8 per 100 PY in TR patients compared to 16.7 and 10.6 per 100 PY in MR patients and those with no or a mild VHD (p<0.01), Figure 1A. The landmark analysis revealed lower one-year mortality in patients who underwent staged TEER compared to those with severe VHD (4.1 vs 12.1 per 100 PY, p<0.001). This trend continued at the five-year follow-up, with a mortality rate of 11.6 per 100 PY in the staged TEER group versus 25.8 per 100 PY in the group with severe VHD (p<0.001), Figure 1B. The multivariate analyses revealed that concomitant severe TR was independently associated with one-year mortality (HR: 1.75 [95% CI: 1.14 – 2.67], p<0.01). Conclusion A concomitant clinically significant VHD was prevalent among patients with AS undergoing TAVR. The persistence of severe VHD was associated with increased one- and five-year mortality following TAVR. Specifically, severe TR was associated with higher mortality rates compared to severe MR. The potential benefit of an additional staged TEER for concomitant VHD should be carefully considered, as it shows promise in improving outcomes for patients with persistent severe VHD after TAVR.

Extending the window in clinical decision making: the role for Impella 5.5 in cardiogenic shock

Abstract Background Acute decompensated heart failure (HF) refractory to medical management deteriorates quickly to cardiogenic shock, ultimately requiring mechanical circulatory support (MCS). These devices aim to provide circulatory support as a bridge to advanced therapies. We report patient outcomes with the latest minimally invasive temporary MCS device: Impella 5.5 with SmartAssist. Methods All patients who underwent Impella 5.5 implantation between January 2020 and December 2023 were analyzed. Duration of Impella support and peri-implant parameters were collected from electronic medical records. ANOVA was performed and utilized a p-value of <0.05 as significant for statistical analysis. Results During our review period, a total of 99 patients were supported with Impella 5.5 in the setting of cardiogenic shock. 92 were bridged to heart transplant (BTT), of which 17 also received combined kidney transplantation. Two underwent durable VAD implantation (BTVAD), and 3 had native heart recovery (BTR) and explant. Two patients died, yielding a survival rate of 98%. For BTT group, the median age was 60 years (52-65) at implant and a median BMI of 27 kg/m² (24-31) with a mean support duration of 29 days (SD ±24). Baseline GFR was 49 mL/min/1.73m² (35-65). In the BTVAD group, the median BMI was 43 kg/m² (39-46) with an average duration of support of 22 days (SD ±8) with a GFR of 55 mL/min/1.73m² (38-73). The BTR group had a median BMI of 29 kg/m² (27-30) with an average duration of support of 15 days (SD ±7) and a lower baseline GFR of 36 mL/min/1.73m² (26 – 37) compared to BTT or BTVAD. The two patients that died were supported for an average of 42 days (SD ±9.2) and expired due to non-candidacy in the setting of newly detected prostate cancer in one patient and multi-organ failure in another. All BTVAD and BTT patients did not have a stroke or major vascular complications before terminal therapy. Conclusion Our center highlights the role of early Impella 5.5 placement in the stabilization of patients in cardiogenic shock, thereby providing both patients and providers time for decision-making while optimizing end-organ perfusion beyond the accepted duration of 14 days.Impella Data - Entire CohortImpella Data - Stratified by Outcome

Cure and Prevention of Cardiovascular Diseases: Herbs for Heart

Context: Cardiovascular diseases (CVDs) account for 30% of deaths worldwide, making them the leading cause of mortality. Prosthetic valve endocarditis (PVE) is a microbial infection that occurs on the surface of a prosthetic valve or on a surgically reconstructed native heart valve. As age increases, the mortality rate from CVDs also rises. Additionally, gender differences were observed, with the mortality rate from cardiovascular disease being higher in women (51%) compared to men (42%). Methods: In this review study, English keywords such as "medicinal plants," "heart," "cardiomyopathy," and "cinnamaldehyde," as well as Persian keywords related to "medicinal plants" and "cardiovascular," were used in the title and abstract of articles. Databases including PubMed, Science Direct, Web of Science, Google Scholar, Scopus, and the academic database of Jihad Daneshgahi were searched without a time limit until March 2021. Results: The results show that several medicinal plants are known to effectively treat CVDs. Conclusions: The findings of this review indicate that medicinal plants have a positive impact on the treatment of cardiovascular diseases and can be considered as potential therapeutic options for managing these conditions.

Sex-related differences in severe native valvular heart disease: the ESC-EORP Valvular Heart Disease II survey.

To assess sex differences in disease characteristics and treatment of patients with severe native valvular heart disease (VHD) included in the VHD II EURObservational Research Programme. A total of 5219 patients were enrolled in 208 European and North African centres and followed for 6 months [41.2% aortic stenosis (AS), 5.3% aortic regurgitation (AR), 4.5% mitral stenosis (MS), 21.3% mitral regurgitation (MR), 2.7% isolated right-sided VHD, 24.9% multiple left-sided VHD]. Indications for intervention were considered concordant if corresponding to class I recommendations specified in the 2012 ESC or 2014 AHA/ACC VHD guidelines. Overall, women were older, more symptomatic, and presented with a higher EuroSCORE II. Bicuspid aortic valve and AR were more prevalent among men while mitral disease, concomitant tricuspid regurgitation (TR), and AS above age 65 were more prevalent among women. On multivariable regression analysis, concordance with recommended treatment was significantly poorer in women with MS and primary MR (both P < .001). Age, patient refusal, and decline of symptoms after conservative treatment were reported significantly more often as reasons to withhold the intervention in females. Concomitant tricuspid intervention was performed at a similar rate in both sexes although prevalence of significant TR was significantly higher in women. In-hospital and 6-month survival did not differ between sexes. (i) Valvular heart disease subtype varied between sexes; (ii) concordance with recommended intervention for MS and primary MR was significantly lower for women; and (iii) survival of men and women was similar at 6 months.

Ten questions about infective endocarditis

Infective endocarditis (IE) is an infective process involving the endocardium and, more frequently, the native heart valves, valvular prostheses and cardiac implantable electronic devices. IE can manifest with various non-specific symptoms making the diagnosis challenging. This condition is associated with high in-hospital and long-term mortality. Therefore, it is particularly important to prevent it by implementing an adequate antibiotic prophylaxis especially in patients at high risk undergoing invasive procedures. Moreover, it is pivotal to promptly diagnose IE, detect the presence of local and systemic complications, establish appropriate antibiotic therapy and identify the indication and timing for surgical treatment. In this focused review, we will provide answers to the most common questions regarding the epidemiology, causes, prophylaxis, diagnosis and antibiotic and surgical treatment of IE.

Folic acid modified silver nanoparticles promote endothelialization and inhibit calcification of decellularized heart valves by immunomodulation with anti-bacteria property

Xenogeneic decellularized heart valves (DHVs) have become one of the most commonly used scaffolds for tissue engineered heart valves (TEHVs) due to extensive resources and possessing the distinct three-layer structure similar to native heart valves. However, DHVs as scaffolds face the shortages such as poor mechanical properties, proneness to thrombosis and calcification, difficulty in endothelialization and chronic inflammatory responses etc., which limit their applications in clinic. In this work, we constructed a novel TEHV with immunomodulatory functions by loading folic acid modified silver nanoparticles (FS NPs) on DHVs to overcome these issues. The FS NPs preferentially targeted M1 macrophages and reduced their intracellular H2O2 level, resulting in polarizing them into M2 phenotype. The increased M2 macrophages facilitated to eliminate inflammation, recruit endothelial cells, and promote their proliferation and endothelialization by secreting relative factors. We founded that FS NPs with the size of 80 nm modified DHVs (FSD-80) performed optimally on cytocompatibility and regulating macrophage phenotype ability in vitro. In addition, the FSD-80 had excellent mechanical properties, hemocompatibility and anti-bacteria property. The results of the subcutaneous implantation in rats revealed that the FSD-80 also had good performance in regulating macrophage phenotype, promoting endothelialization, remolding the extracellular matrix and anti-calcification in vivo. Therefore, FS NPs-loaded DHVs possess immunomodulatory functions, which is a feasible and promising strategy for constructing TEHVs with excellent comprehensive performance.

Clinical Characteristics and Outcomes of Patients Suffering Acute Decompensated Heart Failure Complicated by Cardiogenic Shock.

Cardiogenic shock (CS) can stem from multiple causes and portends poor prognosis. Prior studies have focused on acute myocardial infarction-CS; however, acute decompensated heart failure (ADHF)-CS accounts for most cases. We studied patients suffering ADHF-CS to identify clinical factors, early in their trajectory, associated with a higher probability of successful outcomes. Consecutive patients with CS were evaluated (N=1162). We studied patients who developed ADHF-CS at our hospital (N=562). Primary end point was native heart survival (NHS), defined as survival to discharge without receiving advanced HF therapies. Secondary end points were adverse events, survival, major cardiac interventions, and hospital readmissions within 1 year following index hospitalization discharge. Association of clinical data with NHS was analyzed using logistic regression. Overall, 357 (63.5%) patients achieved NHS, 165 (29.2%) died, and 41 (7.3%) were discharged post advanced HF therapies. Of 398 discharged patients (70.8%), 303 (53.9%) were alive at 1 year. Patients with NHS less commonly suffered cardiac arrest, underwent intubation or pulmonary artery catheter placement, or received temporary mechanical circulatory support, had better hemodynamic and echocardiographic profiles, and had a lower vasoactive-inotropic score at shock onset. Bleeding, hemorrhagic stroke, hemolysis in patients with mechanical circulatory support, and acute kidney injury requiring renal replacement therapy were less common compared with patients who died or received advanced HF therapies. After multivariable adjustments, clinical variables associated with NHS likelihood included younger age, history of systemic hypertension, absence of cardiac arrest or acute kidney injury requiring renal replacement therapy, lower pulmonary capillary wedge pressure and vasoactive-inotropic score, and higher tricuspid annular plane systolic excursion at shock onset (all P<0.05). By studying contemporary patients with ADHF-CS, we identified clinical factors that can inform clinical management and provide future research targets. Right ventricular function, renal function, pulmonary artery catheter placement, and type and timing of temporary mechanical circulatory support warrant further investigation to improve outcomes of this devastating condition.

Pulmonary artery banding to treat end-stage heart failure in infants and young children: A multicenter study

BackgroundConventional treatment options for end-stage heart failure (ESHF) in children include heart transplantation (HT) and ventricular assist device (VAD), both with significant drawbacks in the pediatric population. Pulmonary artery banding (PAB) strategy embedded in a protective cardiovascular drug regime has been effectively used for functional cardiac regeneration and as a bridge to HT in pediatric ESHF.We herein describe the early and mid-term clinical outcomes from a multicenter international experience. MethodsThis is a multicenter retrospective study including children admitted for ESHF caused by dilated cardiomyopathy of any etiology, who were treated with PAB. The primary outcome was the freedom from death/VAD/HT. Data are summarized as median (interquartile range) and count and percentages. Results31 patients (median age 210 days [131-357]) with ESHF underwent PAB in 5 centers. PEDIMACS score was I-III in 90%; 15 patients were intubated preoperatively. Preoperative left ventricular (LV) ejection fraction was <30% in 68%, with LV dilation in all cases. Postoperatively, median PAB gradient was 29 mmHg (23-34), and complications occurred in 14 patients (45%), with 4 (13%) early deaths. Twenty-seven patients were successfully discharged home on cardiac protective medical therapy. At a median follow-up of 2.9 years, there were 1 late death and 3 HTs. Freedom from death/VAD/HT was 77.3% (95% confidence interval [CI]=58-88.4%), 77.3% (95%CI=58-88.4%), and 73.2% (95%CI=53.2-85.5%) at 6 months, 1 year, and 2 years of follow-up, respectively. All 23 survivors with a native heart had gradual normalization of LV function and dimensions. ConclusionsPAB can be an effective procedure to treat ESHF in selected infants, as an innovative conservative strategy for bridging to transplant or recovery.

Role of 3D transoesophageal echocardiography in the study of infective endocarditis. Demonstration in a case collection.

Infective endocarditis (IE) is a condition that predominantly affects native or prosthetic heart valves, which is currently on the rise due to the increase in invasive cardiology procedures, such as the utilization of cardiac implantable electronic devices and transcatheter interventions. The recommended imaging tests for diagnosis are 2D transthoracic echocardiography (2D TTE) and 2D transoesophageal echocardiography (2D TOE). However, these modalities present limitations in detecting vegetations and estimating their dimensions. These disadvantages can be overcome by 3D transoesophageal echocardiography (3D TOE), particularly with the multiplanar reconstruction tool, which allows for the visualization of infinite valve planes, thus optimizing the detection of lesions and precise measurements. Furthermore, the volume rendering provides insight into the anatomical relationships between lesions, which is particularly useful for surgical planning. In this review, we aim to discuss the role of this recent imaging modality in the diagnosis, prognosis, and therapeutic of IE. Finally, we present a collection of images that illustrate the use of 3D TOE tools.

Native Infective Endocarditis: A State-of-the-Art-Review.

Native valve infective endocarditis (NVE) is a global phenomenon, defined by infection of a native heart valve and involving the endocardial surface. The causes and epidemiology of the disease have evolved in recent decades, with a doubling of the average patient age. A higher incidence was observed in patients with implanted cardiac devices that can result in right-sided infection of the tricuspid valve. The microbiology of the disease has also changed. Previously, staphylococci, which are most often associated with health-care contact and invasive procedures, were the most common cause of the disease. This has now been superseded by streptococci. While innovative diagnostic and therapeutic strategies have emerged, mortality rates have not improved and remain at 30%, which is higher than that for many cancer diagnoses. The lack of randomized trials and logistical constraints impede clinical management, and long-standing controversies such as the use of antibiotic prophylaxis persist. This state of the art review addresses clinical practice, controversies, and strategies to combat this potentially devastating disease. A multidisciplinary team will be established to provide care for patients with presumptive NVE. The composition of the team will include specialists in cardiology, cardiovascular surgery, and infectious disease. The prompt administration of combination antimicrobial therapy is essential for effective NVE treatment. Additionally, a meticulous evaluation of each patient is necessary in order to identify any indications for immediate valve surgery. With the intention of promoting a more comprehensive understanding of the procedural management of native infective endocarditis and to furnish clinicians with a reference, the current evidence for the utilization of distinct strategies for the diagnosis and treatment of NVE are presented.

Measurement of left ventricular volume with admittance incorporated onto percutaneous ventricular assist device.

Percutaneous ventricular assist devices (pVADs) incorporated with admittance electrodes have been validated in animal studies for accurate instantaneous volumetric measurements. Since miniaturization of the pVAD profile is a priority to reduce vascular complications in patients, our study aimed to validate admittance measurements using three electrodes instead of the standard four. Complex admittance was measured between an electrode pair and a pVAD metallic blood-intake tip, both with finite element analysis and on the benchtop. The catheter and electrode arrays were first simulated inside prolate ellipsoid models of the left ventricle (LV) demonstrating current flow throughout all parts of the LV as well as minimal influence of off-center catheter placement in the recorded signal. Admittance measurements were validated in 3D-printed models of healthy and dilated hearts (100-400mL end-diastolic volumes). Minimal interference between a pVAD motor and the current signal of our admittance system was demonstrated. A modified Wei's equation focused on three electrodes was developed to be compatible with reduced profile pVADs occurring clinically, incorporated with admittance electrodes and wires. The modified equation was compared against Wei's original equation showing improved accuracy of calculated volumes. Reducing electrode footprint can simplify the incorporation of Admittance technology on any pVAD, allowing for instantaneous recognition of native heart recovery and assistance with pVAD weaning.

Cardiac power output ratio: Novel survival predictor after percutaneous ventricular assist device in cardiogenic shock.

Currently, there is limited data on prognostic indicators after insertion of percutaneous ventricular assist device (PVAD) in the treatment of cardiogenic shock (CS). This study evaluated the prognostic role of cardiac power output (CPO) ratio, defined as CPO at 24h divided by early CPO (30min to 2h), in CS patients after PVAD. Consecutive CS patients from the QEH-PVAD Registry were followed up for survival at 90days after PVAD. Among 121 consecutive patients, 98 underwent right heart catheterization after PVAD, with CPO ratio available in 68 patients. The CPO ratio and 24-h CPO, but not the early CPO post PVAD, were significantly associated with 90-day survival, with corresponding area under curve in ROC analysis of 0.816, 0.740, and 0.469, respectively. In multivariate analysis, only the CPO ratio and lactate level at 24h remained as independent survival predictors. The CPO ratio was not associated with age, sex, and body size. Patients with lower CPO ratio had significantly lower coronary perfusion pressure, worse right heart indices, and higher pulmonary vascular resistance. A lower CPO ratio was also significantly associated with mechanical ventilation and higher creatine kinase levels in myocardial infarction patients. In post-PVAD patients, the CPO ratio outperformed the absolute CPO values and other haemodynamic metrics in predicting survival at 90days. Such a proportional change of CPO over time, likely reflecting native heart function recovery, may help to guide management of CS patients post-PVAD.

Obstructions of prosthetic heart valves: diagnosis and treatment considerations

Objectives: Since the first years of native heart valve replacement by - prosthetic valves; prosthesis thrombogenicity has kept its importance as a serious problem causing post-operative morbidities and mortality. This study aims to evaluate early postoperative morbidity and mortality of patients diagnosed with prosthetic valve thrombosis and treated surgically or non-surgically. Methods: Thirty-one patients diagnosed with and treated for prosthetic valve thrombosis were evaluated retrospectively. The patients were followed up for 58 months. Results: There were 24 females and 7 males. The mean patient age at the time of prosthetic valve thrombosis diagnosis was 40.7±11 (range, 10-57) years. The mean duration between prosthetic valve replacement and the first signs of prosthetic valve thrombosis was 67.67±66 (range, 1 to 300) months. All patients presented with a functional capacity of NYHA Class III or IV. A total of 32 interventions; 27 surgical and 5 thrombolytic treatments due to elevated aortic prosthetic valve pressure gradient which did not improve with thrombolysis. Of 27 surgical interventions for thrombosed prosthetic valves, 21 involved mitral, 2 aortic, and 4 tricuspid positions. A total of 9 patients died during follow-up. The overall mortality rate was 29.03%. The mortality rate was 29.62% after surgical interventions and 20% after thrombolytic treatment. Conclusion: Currently prosthetic valve replacement is the basic palliation method in the management of patients with diseased native heart valves. In the majority of mechanical prosthetic valve obstructions, the main pathology is fibrous tissue proliferation-related to irregular warfarin usage, which in turn causes the development of acute symptoms secondary to acute valve thrombosis. The necessary treatment method for prosthetic valve obstructions should be either the use of thrombolytic agents or the replacement of the obstructed prosthetic valve with a new one.

Prolonged Impella 5.0/5.5 support within different pathways of care for cardiogenic shock: the experience of a referral center.

Impella 5.0 and 5.5 are promising low-invasive left ventricle (LV) temporary mechanical circulatory supports (tMCS) for cardiogenic shock due to LV mechanical unloading and are paired with powerful hemodynamic support. This study aimed to analyze data and destinies of patients supported with Impella 5.0/5.5 at a national referral center for cardiogenic shock and to assess the parameters associated with myocardial recovery and successful weaning. A single-center observational study was conducted on all patients treated with Impella 5.0 or 5.5 from March 2018 to July 2023. A total of 59 patients underwent Impella 5.0/5.5 implantation due to profound cardiogenic shock, with acute myocardial infarction being the most frequent cause of shock (42 patients, 71%). The median duration of Impella support was 13 days (maximum duration of 52 days). Axillary cannulation was feasible in almost all patients, and 36% were mobilized during support. A total of 44 patients (75%) survived to the next therapy/recovery: 21 patients experienced recovery and 15 and 8 were bridged to long-term LVAD and heart transplantation, respectively. The global survival rate was 66%. The predictors of native heart recovery at multivariate analysis were the number of days on tMCS before upgrade to Impella 5.0/5.5 [hazard ratio (HR) 0.68 (0.51-9) p = 0.0068] and improvement of LVEF within the first 7-10 days of support [HR 4.72 (1.34-16.7), p = 0.016]. Transcatheter systems such as Impella 5.0/5.5 revolutionized the field of tMCS. Myocardial recovery is the primary clinical target. Its prognostication and promotion are key to ensure the most proficuous course for each patient from cardiogenic shock to long-term event-free survival.

Gross morphology and morphometry of native and decellularized heart valves of caprine: A comparative study.

The gross morphological examination of native caprine heart valves revealed distinctive structural characteristics of the caprine's cardiac anatomy. Four primary orifices were identified, each protected by thin, valve-like structures. Atrioventricular orifices featured tricuspid and bicuspid valves, while the aorta and pulmonary arteries were guarded by semilunar valves. Within the atrioventricular apparatus, distinct features were observed including the tricuspid valve's three leaflets and the bicuspid valve's anterior and posterior leaflets. Ultrasonography provided insights into valve thickness and chordae tendineae lengths. Morphometric studies compared leaflets/cusps within individual native valves, showcasing significant variations in dimensions. Comparative analysis between native and decellularized valves highlighted the effects of decellularization on leaflet thickness and chordae tendineae lengths. Decellularized valves exhibited reduced dimensions compared to native valves, indicating successful removal of cellular components. While some dimensions remained unchanged post-decellularization, significant reductions were observed in leaflet thicknesses and chordae tendineae lengths. Notably, semilunar valve cusps displayed varying responses to decellularization, with significant reductions in cusp lengths observed in the aortic valve, while the pulmonary valve exhibited more subtle changes. These findings underscore the importance of understanding structural alterations in heart valves post-decellularization, providing valuable insights for tissue engineering applications and regenerative medicine.

Clinical outcomes among cardiogenic shock patients supported with high-capacity Impella axial flow pumps: A report from the Cardiogenic Shock Working Group

BackgroundThe Impella 5.0 and 5.5 pumps (Abiomed, Danvers, MA) are large-bore transvalvular micro-axial assist devices used in cardiogenic shock (CS) for patients requiring high-capacity flow. Despite their increasing use, real-world data regarding indications, rates of utilization and clinical outcomes with this therapy are limited. ObjectivesTo examine clinical profiles and outcomes of patients in a contemporary, real-world CS registry of patients who received an Impella 5.0/5.5 alone or in combination with other temporary mechanical circulatory support (tMCS) devices. MethodsThe CS Working Group (CSWG) Registry includes patients from 34 US hospitals. For this analysis, data from patients who received an Impella 5.0/5.5 between 2020-2023 were analyzed. Use of Impella 5.0/5.5 with or without additional tMCS therapies, duration of support, adverse events and outcomes at hospital discharge were studied. Adverse events including stroke, limb ischemia, bleeding and hemolysis were not standardized by the registry but reported per individual CSWG Primary Investigator discretion. For those who survived, rates of native heart recovery (NHR) or heart replacement therapy (HRT) including heart transplant (HT), or durable ventricular assist device (VAD) were recorded. We also assessed outcomes based on based on shock etiology (acute myocardial infarction or MI-CS vs. heart failure-related CS or HF-CS). ResultsAmong 6,205 patients, 754 received an Impella 5.0/5.5 (12.1%), including 210 MI-CS (27.8%) and 484 HF-CS (64.1%) patients. Impella 5.0/5.5 was used as the sole tMCS device in 32% of patients, while 68% of pts received a combination of tMCS devices. Impella cannulation sites were available for 524/754 (69.4%) of patients, with 93.5% axillary configuration. Survival to hospital discharge for those supported with an Impella 5.0/5.5 was 67%, with 20.4% NHR and 45.5% HRT. Compared to HF-CS, patients with MI-CS supported on Impella 5.0/5.5 had higher in-hospital mortality (45.2% vs 26.2%, p<0.001) and were less likely to receive HRT (22.4% vs 56.6%, p<0.001. For patients receiving a combination of tMCS during hospitalization, this was associated with higher rates of limb ischemia (9% vs. 3%, p<0.01), bleeding (52% vs. 33%, p<0.01), and mortality (38% vs 25%; p<0.001) compared to Impella 5.0/5.5 alone. Among Impella 5.5 recipients, the median duration of pump support was 12.9 days (IQR: 6.8-22.9) and longer in patients bridged to HRT (14 days; IQR: 7.7-28.4). ConclusionsIn this multi-center cohort of patients with CS, use of Impella 5.0/5.5 was associated with an overall survival of 67.1% and high rates of HRT. Lower adverse event rates were observed when Impella 5.0/5.5 was the sole support device used. Further study is required to determine whether a strategy of early Impella 5.0/5.5 use for CS improves survival. Condensed abstractHigh capacity Impella heart pumps provide up to 5.5 L/min of flow, while axillary surgical cannulation allows for ambulation. Patients with advanced cardiogenic shock from acute myocardial infarction or heart failure requiring temporary mechanical circulatory support may benefit from upfront use of Impella 5.5 to improve overall survival, including native heart recovery or successful bridge to durable left ventricular assist device surgery or heart transplantation, and to reduce adverse event rates.

Mechanical load regulates the proliferation of multiple cell types in the heart

Abstract Funding Acknowledgements None. Introduction The adult mammalian heart has a poor regenerative and angiogenic potential. At the same time, both primary cardiac tumors and cardiac metastases are extremely rare. This suggests that shared mechanisms may halt the proliferation of cardiac (both cardiomyocyte and endothelial) and cancer cells. Among the mechanisms that have been claimed to be responsible for the loss of proliferative potential of cardiomyocytes early after birth is a sudden increase in mechanical load. Purpose Here, we investigate whether alterations in mechanical load affect the proliferation of multiple cell types in the heart. Methods Adult heart unloading in vivo was achieved using a mouse model of heterotopic heart transplantation, followed by EdU injection to label proliferating cells. Engineered heart tissues (EHTs) were generated using neonatal cardiomyocytes and fibroblasts, with a modified protocol allowing to finely tune mechanical load. Primary cardiac endothelial cells and multiple types of cancer cells (lung, melanoma and colon cancer) along with adult cardiac endothelial cells were included in EHTs. Results In line with our hypothesis, unloaded, heterotransplanted hearts showed a significant number of proliferating cardiomyocytes and endothelial cells, which were almost absent in native hearts. While cancer cells did not grow in native hearts, they massively proliferated in unloaded hearts. Consistent with in vivo results, mechanical unloading in EHTs significantly increased the percentage of EdU-positive cardiomyocytes, endothelial and cancer cells. In contrast, increasing afterload reduced cell proliferation in all cell types. Mechanistically, we identified Nesprin2 as an essential factor in sensing mechanical load and translating it into a cell proliferation arrest. Conclusions Overall, these data indicate that variations in mechanical load have a dramatic effect on the proliferation of multiple cell types within the heart tissue, including cardiomyocytes, endothelial and cancer cells and that Nesprin2 is required to mediate this effect.Unloading in the heartUnloading in EHT

Reduced Graphene-Oxide-Doped Elastic Biodegradable Polyurethane Fibers for Cardiomyocyte Maturation.

Conductive biomaterials offer promising solutions to enhance the maturity of cultured cardiomyocytes. While the conventional culture of cardiomyocytes on nonconductive materials leads to more immature characteristics, conductive microenvironments have the potential to support sarcomere development, gap junction formation, and beating of cardiomyocytes in vitro. In this study, we systematically investigated the behaviors of cardiomyocytes on aligned electrospun fibrous membranes composed of elastic and biodegradable polyurethane (PU) doped with varying concentrations of reduced graphene oxide (rGO). Compared to PU and PU-4%rGO membranes, the PU-10%rGO membrane exhibited the highest conductivity, approaching levels close to those of native heart tissue. The PU-rGO membranes retained anisotropic viscoelastic behavior similar to that of the porcine left ventricle and a superior tensile strength. Neonatal rat cardiomyocytes (NRCMs) and human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) on the PU-rGO membranes displayed enhanced maturation with cell alignment and enhanced sarcomere structure and gap junction formation with PU-10%rGO having the most improved sarcomere structure and CX-43 presence. hiPSC-CMs on the PU-rGO membranes exhibited a uniform and synchronous beating pattern compared with that on PU membranes. Overall, PU-10%rGO exhibited the best performance for cardiomyocyte maturation. The conductive PU-rGO membranes provide a promising matrix for in vitro cardiomyocyte culture with promoted cell maturation/functionality and the potential for cardiac disease treatment.

ENDOCARDITIS TEAM? DESIGNING AN ORIGINAL AND TAILORED CLINICAL PATHWAY

Abstract Infective endocarditis (IE) remains a poorly understood disease that primarily affects either native or prosthetic heart valves. Its incidence has increased over the past two decades, now affecting 3 to 10 individuals per 100.000/year in the general population. Despite advances in early diagnosis and surgical intervention, IE continues to pose a significant challenge, often leading to severe complications and carrying a substantial burden of morbidity and mortality. Data from the EURO–Endo registry show a drastic change in IE and provide an accurate picture of IE disease today. In European countries, it tends to affect older patients with a remarkable 12% of cases occurring in those aged ≥ 80 years. The traditional care pathway is often fragmented into multiple and potentially dangerous steps, resulting in delayed diagnosis and treatment. Such a “patchy” approach may cause suboptimal patient management, especially in the subset of frail patients with important concomitant diseases and high surgical risk. Clinical pathways (CPs) are an evidence–based multidisciplinary care plans involving diagnosis, treatment and rehabilitation phases, through which to follow patients from hospital admission to discharge, in order to manage a specific health condition, aiming to optimize patient and hospital/team outcomes, while contributing to a better organized care processes. In 2018, a working group composed by healthcare managers, infectious disease specialists, cardiac surgeons, cardiologists, anesthesiologists, geriatricians and other professionals involved in the care of IE patients have engineered a dedicated CP for IE at our institution. The CP introduced significant changes in the management of patients with IE. As a result, the quality of care and services offered increased, a faster and more appropriate diagnosis and treatment were achieved, patient outcomes and safety improved and a better coordination and continuity of care between different settings was guaranteed. The growing burden of IE in western countries demands an evidence–based multidisciplinary care plan. The creation of a territorial network ensures continuity and appropriateness of care in conjunction with the referring physicians/hospital and rationalization of resources. Although some controversies still exist, we believe that CP will have a positive impact on quality in health care.

Storytelling of Myocarditis.

In 1900, Fiedler first reported autopsy cases with peculiar inflammation of the myocardium, which he named interstitial myocarditis. He postulated an isolated cardiac inflammation of the myocardium in the absence of multiorgan involvement and with a poor prognosis due to invisible microorganisms, which years later would have been identified as viruses. The revision of original histologic sections by Schmorl showed cases with lymphocytes and others with giant-cell inflammatory histotypes. The in vivo diagnosis of myocarditis became possible thanks to right cardiac catheterization with endomyocardial biopsy (EMB). The gold standard for diagnosis was achieved with the employment of immunohistochemistry and molecular investigation by Polymerase Chain Reaction (PCR), which allows for the detection of viruses as causal agents. Both RNA and DNA were revealed to be cardiotropic, with a common receptor (CAR). A protease, coded by coxsackie virus, disrupts the cytoskeleton and accounts for cell death. Unfortunately, vaccination, despite having been revealed to be effective in animal experiments, has not yet entered the clinical field for prevention. Cardiac Magnetic Resonance turned out to be a revolutionary tool for in vivo diagnosis through the detection of edema (inflammatory exudate). Myocarditis may be fulminant in terms of clinical presentation but not necessarily fatal. The application of ExtraCorporeal Membrane Oxygenation (ECMO) allows for relieving the overloaded native heart.