Search Results (74)

Although experimental evidence indicates that mitochondrial collapse is a common effect of both Chagas disease and post-ischemic heart failure and that cardiac anatomy and function are partially restored by stem cell therapy, the responsible molecular mechanisms are still under debate. Gene expression data from our publicly accessible transcriptomic dataset obtained by profiling the left ventricle myocardia of mouse models of Chagas disease and post-ischemic heart failure were re-analyzed from the perspective of the Genomic Fabric Paradigm. In addition to the regulation of the gene expression levels, we determined the changes in the strength of the homeostatic control of transcript abundance and the remodeling of the gene networks responsible for the mitochondrial respiration. The analysis revealed that most of the mitochondrial genes assigned to the five complexes of the respiratory chain were significantly downregulated by both Chagas disease and ischemia but exhibited outstanding recovery of the normal expression levels following direct injection of bone-marrow-derived stem cells. However, instead of regaining the original expression control and gene networking, the treatment induced novel mitochondrial arrangements, suggesting that multiple transcriptomic topologies might be compatible with any given physiological or pathological state. This study confirmed several established mechanisms and identified novel gene expression signals, especially Cox4i2, Cox6b1, Cox7b, Ndufb11, and Tmem186, that warrant further investigations. Their broad rescue with cell therapy underscores mitochondria as a convergent, tractable target for cardiac repair. Full article

Background: Atrial fibrillation (AF) may be detected at the time of ischemic stroke or newly detected after stroke. While AF detected after stroke (AFDAS) is associated with poor outcomes compared to sinus rhythm, its prognostic implications relative to known-AF are inconsistent. High-sensitivity cardiac troponin (hs-cTn) is a biomarker of myocardial injury, but its role in predicting AFDAS in stroke patients is unclear. We aimed to evaluate hs-cTn as a predictor for AFDAS and to compare all-cause death, readmission for heart failure (HF) and readmission for stroke among patients with non-AF, AFDAS, and known-AF in the post-ischemic stroke period. Methods: From August 2014 to July 2017, 1506 patients with acute ischemic stroke were consecutively enrolled in a retrospective single-center registry. Out of these, 1019 patients were selected for analysis. The primary outcome was major adverse cardiac and cerebrovascular events (MACCE), a composite of all-cause death, HF-caused readmission, or stroke-caused readmission during follow-up. Results: Out of 1019 ischemic stroke patients, 121 (13.8%) developed AFDAS over a median of 22.5 months; 135 had known-AF and 763 were maintained sinus rhythm during follow-up. Elevated hs-TnI (≥99th percentile), age > 75, and left atrial volume index >34 mL/m² independently predicted AFDAS. Both AFDAS and known-AF groups had a significantly increased risk of MACCE compared to the non-AF group (adjusted hazard ratio (HR) 1.85 and 1.76, respectively; p < 0.05 for both). The known-AF group also had a higher risk of all-cause mortality (adjusted HR 2.05, p = 0.02). The risks for MACCE and all-cause death did not differ significantly between the AFDAS and known-AF groups. Conclusions: An elevated hs-TnI level is independently associated with development of AFDAS and may serve as a valuable marker for stratifying the risk of future cerebrocardiovascular events following ischemic stroke. Full article

Background and Objectives: Normothermic ex situ heart preservation maintains donor heart viability by sustaining physiological conditions and reducing ischemic damage. However, the ideal perfusion pressure remains uncertain. This study aims to identify the optimal perfusion pressure to enhance graft preservation in rat heart transplantation. Materials and Methods: We utilized 20 male Sprague-Dawley rats (400–500 g). Donor hearts underwent normothermic preservation for 2 h using a Langendorff apparatus primed with 12 mL of solution at a consistent 3 mL/min flow. After preservation, hearts were transplanted heterotopically into the recipient’s abdomen. We defined successful preservation by observing a QRS complex in electrocardiographic monitoring for 3 h post-transplantation. Histological assessments for myocardial integrity occurred after 4 h of reperfusion. We analyzed statistical differences between successful and unsuccessful preservation groups. Results: Electrocardiograms indicated preservation failure in 8 of the 20 donor hearts due to the absence of a QRS complex. We observed no significant differences in ischemic duration between groups. At 120 min, although serum lactate and potassium concentrations increased in the unsuccessful group, the differences were not statistically significant. Higher initial perfusion pressures (>65 mmHg) at a constant flow rate resulted in elevated lactate and potassium concentrations post-preservation, indicating suboptimal outcomes. Histologically, hematoxylin and eosin staining showed better myocardial preservation in successful hearts, while TUNEL assays demonstrated increased apoptosis in unsuccessful hearts. All hearts increased in weight after preservation, but significant increases occurred only in unsuccessful cases. Conclusions: Higher initial perfusion pressures (>65 mmHg) negatively affect heart preservation outcomes, resulting in elevated serum lactate and potassium levels, increased heart weight, and greater histological damage. Maintaining optimal perfusion pressures is essential to preserve myocardial integrity and functional viability during normothermic ex situ heart preservation. Full article

Background: Autonomic dysfunction is commonly encountered after acute ischemic stroke (AIS) and may influence both functional recovery and survival. Heart rate variability (HRV) provides a non-invasive measure of autonomic balance, but its temporal evolution and prognostic significance in AIS remain insufficiently evaluated. Methods: In this prospective observational study, 148 AIS patients (mean age of 65.93 ± 9.19 years) underwent HRV assessment at baseline, one month, and three months follow-up, between January 2022 and October 2024. Time and frequency domain parameters, including Standard Deviation of NN intervals (SDNN), Low-Frequency (LF) power, High-Frequency (HF) power, and LF/HF ratio, were analyzed. Functional outcome was assessed using the modified Rankin Scale (mRS), with a good outcome defined as mRS ≤ 2. Multivariable logistic regression identified independent predictors of poor outcome (mRS > 2) at each time point. Mortality was recorded at one and three months, and potential predictors were evaluated. Results: Over three months, SDNN increased by 34.84% (p < 0.001), HF power rose by 22.26% (p < 0.001), LF power decreased by 21.61% (p < 0.001), and LF/HF ratio declined by 35.41% (p < 0.001), indicating a shift toward parasympathetic predominance. Higher SDNN correlated strongly with better functional status and was an important predictor of favorable outcome at all time points (p < 0.001). Higher LF/HF ratio predicted poor outcome at baseline (p < 0.01) and three months (p < 0.001). At three months, mortality reached 12.2%, with significant predictors including coronary artery disease (CAD), heart failure (HF), chronic kidney disease (CKD), and altered HRV parameters. Conclusions: Post-stroke recovery is characterized by the progressive restoration of autonomic balance, with higher SDNN and lower LF/HF associated with improved functional recovery and survival. HRV analysis offers valuable prognostic insight and may aid in risk stratification after AIS. Full article

Background: Patients in cardiogenic shock (CS) often require prolonged mechanical circulatory support lasting longer than 14 days. Prolonged support with Impella 5.5 can improve outcomes in these patients. Here, we describe our experience with prolonged Impella 5.5 support. Methods: From January 2023 to June 2024, 64 patients receiving Impella 5.5 support for more than 14 days were identified. Information including demographics, heart failure etiology, and hospital course were collected. Results: Of the 64 patients identified, 54 were male, with an average age of 55.9 years. One patient was classified as SCAI class C, 41 as SCAI class D, and 22 as SCAI class E. Heart failure etiologies included 41 patients with non-ischemic cardiomyopathy, 10 with ischemic cardiomyopathy, 10 with acute myocardial infarction, 1 with cardiac allograft rejection, 1 with post-cavotricuspid isthmus ablation, and 1 with post-cardiotomy (aortic root replacement) CS. The average duration of Impella 5.5 support was 27.1 days. Escalation to Impella 5.5 was observed in 26 patients, with 15 having escalated from intra-aortic balloon pump and 11 from Impella CP. Overall survival, including heart recovery, orthotopic heart transplantation (OHT), or left ventricular assist device (LVAD), was 81.3% (52/64) in patients with Impella 5.5. Patients were discharged after OHT (27/64), cardiac recovery (13/64), or durable LVAD placement (12/64), and 12 patients expired. Conclusions: Our data suggest that Impella 5.5 provides durable support for patients beyond the 14-day period currently approved by the FDA for CS management. Further evaluation of long-term Impella 5.5 support for cardiac recovery or as a bridge to advanced therapies should be considered. Full article

Pathologies of the heart (e.g., ischemic disease, valve fibrosis and calcification, progressive myocardial fibrosis, heart failure, and arrhythmogenic disorders) stem from the irreversible deterioration of cardiac tissues, leading to severe clinical consequences. The limited regenerative capacity of the adult myocardium and the architectural complexity of the heart present major challenges for tissue engineering. However, recent advances in biomaterials and biofabrication techniques have opened new avenues for recreating functional cardiac tissues. Particularly relevant in this context is the integration of biomimetic design principles, such as structural anisotropy, mechanical and electrical responsiveness, and tissue-specific composition, into 3D bioprinting platforms. This review aims to provide a comprehensive overview of current approaches in cardiac bioprinting, with a focus on how structural and functional biomimicry can be achieved using advanced hydrogels, bioprinting techniques, and post-fabrication stimulation. By critically evaluating materials, methods, and applications such as patches, vasculature, valves, and chamber models, we define the state of the art and highlight opportunities for developing next-generation bioengineered cardiac constructs. Full article

Background: This study investigates the potential mechanisms behind changes in cardiac structure and function in long COVID patients. Methods: This study involved 176 consecutive outpatients in follow-up care (average age 55.9 years; 58.5% male) who experienced symptoms for over 12 weeks (average 6.2 ± 2.7 months), following coronavirus infection (COVID-19). Results: The patients with long COVID and cardiovascular manifestations were significantly more hospitalized (88.5% vs. 75.9%) and had longer hospital stays. Significant echocardiography changes were observed in the left ventricular ejection fraction (LVEF) (59.6 ± 5.4% vs. 62.5 ± 3.8%); longitudinal strain (LS) in the sub-endocardium and intra-myocardium layers (−20.9 vs. −22.0% and −18.6 vs. −19.5%); circumferential strain (CS) in the sub-epicardium layers (−9.6 vs. −10.5%); and CS post-systolic shortening (CS PSS) (0.138 vs. 0.088 s). Additionally, pathological cardiac magnetic resonance (CMR) findings were seen in 58.2% of the group of patients with long COVID and cardiovascular manifestation; 43.3% exhibited positive late gadolinium enhancement (LGE), 21.0% had elevated native T1 mapping, and 22.4% had elevated native T2 mapping. Conclusions: Most patients with long COVID showed structural and functional changes in their cardiovascular systems, primarily caused by prolonged inflammation. Using multimodality imaging is important for uncovering the mechanisms to predict chronic myocarditis, early-stage heart failure, and pre-ischemic states, which can lead to serious complications. Recognizing the specific cardiovascular phenotypes associated with long COVID is essential in order to provide timely and appropriate treatment. Full article

Background: The HeartMate 3 (HM3) left ventricular assist device (LVAD) has demonstrated improved clinical outcomes in patients with advanced heart failure (HF). However, the influence of underlying HF etiology—ischemic cardiomyopathy (ICM) versus dilated cardiomyopathy (DCM)—on post-implantation outcomes remains insufficiently characterized. Objectives: This paper aims to evaluate early postoperative outcomes following HM3 LVAD implantation in patients with ICM versus DCM and to identify the preoperative hemodynamic and clinical predictors of early mortality and hemodynamic instability. Methods: We conducted a retrospective single-center cohort study of 30 patients who underwent HM3 LVAD implantation between 2017 and 2024. Patients were stratified by HF etiology (ICM, n = 17; DCM, n = 13), and preoperative clinical, echocardiographic, and right heart catheterization data were analyzed. The primary endpoint was 30-day postoperative survival. Secondary endpoints included postoperative hemodynamic stability and the need for vasopressor support. Results: Non-survivors (n = 13) demonstrated elevated central venous pressure (>16.5 mmHg), mean right ventricular pressure (>31.5 mmHg), and pulmonary vascular resistance (>7.5 Wood units), in addition to higher preoperative creatinine levels and longer cardiopulmonary bypass times. Vasopressor requirement postoperatively was associated with elevated pre-implant systolic pulmonary artery pressure. Conclusions: Preoperative right-sided pressures and renal dysfunction are strong predictors of early mortality following HM3 LVAD implantation. Patients with ICM exhibit greater early left ventricular recovery compared to those with DCM. These findings underscore the importance of comprehensive and personalized preoperative risk stratification—particularly in patients with DCM and pulmonary hypertension—to optimize postoperative outcomes and guide patient selection for durable LVAD support. Full article

Myocardial infarction (MI) is a leading cause of morbidity worldwide, resulting from ischemic damage and necrosis to cardiomyocytes. While the standard treatment regimen for MI can be successful in restoring coronary perfusion, it typically does not resolve myocardial damage, which can leave patients particularly vulnerable to complications such as heart failure or electrical conduction abnormalities. Stem cell therapies offer a promising novel approach aimed at restoring cardiac function and decreasing the incidence of functional complications after an MI. This review used a literature search to evaluate the current landscape of stem cell therapy for post-MI recovery and focuses on the stem cell candidates for MI recovery therapy, delivery methods of such treatment, and their effectiveness. Both preclinical and clinical trials have demonstrated the safety of stem cells, but have struggled with limited cell retention, inconsistent efficacy, and survival. Mechanisms are employed by stem cells to promote regeneration, such as paracrine signaling, angiogenesis, and structural remodeling, in addition to the various stem cell delivery methods, including intracoronary infusion, direct myocardial injection, and intravenous administration. Furthermore, some strategies to combat past challenges in this field are discussed; for instance, extracellular vesicles, bioengineered patches, hydrogels, gene editing, and bioprinting. This article will provide a framework for future research in stem cell therapies and highlight the current progress in the field. Full article

Background: Sepsis survivors are at risk of developing myocardial infarction and heart failure. It remains unclear whether coronary artery disease (CAD) is a major contributor to the development of these complications. This study sought to characterize the burden and distribution of significant CAD in sepsis survivors. Methods: Sepsis survivors who underwent computed tomography coronary angiography (CTCA) or invasive coronary angiography (ICA) in a UK tertiary cardiac center for suspected ischemic heart disease were retrospectively studied. Results: Of the 30 sepsis survivors (age 57 ± 12 years; 50% males), 21 patients underwent CTCA and 9 patients underwent ICA a median 39 days [IQR 12–152] from the sepsis episode. Eight patients (~27%) had angiographically significant CAD (n = 6 severe [>70%] stenosis; n = 2 moderate [50–70%] stenosis). The CT coronary calcium score was higher in patients with significant CAD compared to patients without significant CAD (638 [368–1015] vs. 4 [1–72]; p < 0.001). Of the 8 patients with significant CAD, 3 patients had LV systolic dysfunction (38%) on echocardiography and 8/21 (38%) patients without significant CAD had LV systolic dysfunction (p = 1.00). Long-term adverse complications (all-cause mortality and/or heart failure hospitalization) occurred 3/8 (38%) patients with significant CAD and 4/22 (18%) patients without significant CAD (p = 0.345). Conclusions: A minority of sepsis survivors have significant CAD. The presence of significant CAD cannot fully explain the occurrence of post-sepsis LV systolic dysfunction and adverse outcomes. The ischemic and non-ischemic mechanisms underlying post-sepsis cardiovascular disease require further investigation. Full article

Background and Objectives: Nonischemic cardiomyopathies comprise a wide spectrum of heart muscle disorders characterized by different morphological, functional, and tissue abnormalities. Cardiovascular magnetic resonance (CMR) represents the gold standard imaging modality for assessing cardiac morphology, systolic function, and tissue characterization, thereby aiding in early diagnosis, precise phenotyping, and tailored treatment. The aim of this review is to provide an up-to-date overview of CMR techniques for studying myocardial perfusion and their applications to nonischemic cardiomyopathy, not only to rule out an underlying ischemic aetiology but also to investigate the pathophysiological characteristics of microcirculatory dysfunction in these patients. Materials and Methods: We performed a structured review of the literature focusing on first-pass gadolinium perfusion sequences, stress protocols, and emerging pixel-wise perfusion mapping approaches. Studies were selected to illustrate the methods for image acquisition, post-processing, and quantification of myocardial blood flow (MBF) and myocardial perfusion reserve (MPR), as well as to highlight associations with clinical endpoints. Results: First-pass CMR perfusion imaging reliably detects diffuse and regional microvascular dysfunction across cardiomyopathies. Semi-quantitative parameters (e.g., upslope, MPRI) and quantitative MBF mapping (mL/g/min) have demonstrated that impaired perfusion correlates with disease severity, extent of fibrosis, and adverse outcomes, including heart failure hospitalization, arrhythmias, and mortality. Novel automated pixel-wise mapping enhances reproducibility and diagnostic accuracy, distinguishing coronary microvascular dysfunction from balanced three-vessel disease. Microvascular dysfunction—present in approximately 50–60% of dilated cardiomyopathy (DCM), 40–80% of hypertrophic cardiomyopathy (HCM), and >95% of cardiac amyloidosis (CA) patients—has emerged as a key driver of adverse outcomes. Perfusion defects appear early, often preceding overt hypertrophy or fibrosis, and provide incremental prognostic value beyond conventional CMR metrics. Conclusions: CMR represents a powerful tool for detecting myocardial perfusion abnormalities in nonischemic cardiomyopathies, improving phenotyping, risk stratification, and personalized management. Further standardization of quantitative perfusion techniques will facilitate broader clinical adoption. Full article

Background/Objectives: The aim of this study was to evaluate the impact of chronic heart failure (CHF), chronic kidney dysfunction (CKD), and the combined CHF-CKD comorbidity on the outcomes of rehabilitation in stroke patients. Methods: A total of 586 patients who had suffered a stroke (mean age, 70 ± 13; 47.6% female; 72.4% ischemic and 27.6% hemorrhagic strokes) and who were admitted immediately after acute stroke care to a rehabilitation center were included in this cohort study and followed up with until their death or discharge from the rehabilitation center. The clinical characteristics of the patients were obtained from their medical records. The relationship between the background comorbidities (CHF, CKD, and concurrent CHF-CKD) and fatal and non-fatal unfavorable outcomes (emergency readmission to a primary hospital or transfer to a long-term care facility in a vegetative or minimally conscious state) were investigated. Results: Unfavorable outcomes were more common in the groups with background CHF and/or CKD. From the Cox multivariate analysis, both CHF and CKD were independent prognostic factors for the occurrence of unfavorable outcomes, with a hazard ratio (HR) of 2.28 (95% CI = 1.2–4.29; p-value = 0.01) and 2.19 (95% CI = 1.24–3.87; p-value = 0.007), respectively. Moreover, the combined CHF-CKD comorbidity showed a more than 5-fold increased risk of an adverse post-stroke outcome (HR of 5.8; 95% CI = 2.5–13.44; p-value < 0.001). Conclusions: The combined CHF-CKD comorbidity is an important independent complicating factor that, along with other known influencing factors, can affect unfavorable post-stroke outcomes more than CHF or CKD alone, and necessitates critical attention to its diagnosis and management as a separate mixed syndrome. Full article

Background: The stroke–heart syndrome refers to incident cardiac complications post stroke. This study aims to evaluate the stroke–heart syndrome by determining the rate and predictors of readmission for cardiac disease within 30 days of hospitalization for cerebral infarction. Methods: Data from the United States Nationwide Readmissions Database (2018 to 2020) were analyzed to identify rates and factors associated with 30-day readmissions for heart disease following cerebral infarction, excluding patients with atrial fibrillation, heart failure and myocardial infarction during admission with cerebral infarction. Results: There were 3,115,850 hospital admissions for cerebral infarction, and 75,440 admissions (2.4%) were readmitted with new onset cardiac events within 30 days of discharge. This included 36,310 (1.4%) readmissions for heart failure, 35,900 (1.1%) readmissions for atrial fibrillation, 17,465 (0.5%) readmissions for acute myocardial infarction, 810 (0.03%) readmissions for ventricular arrhythmias and 700 (0.02%) readmissions for Takotsubo syndrome. Readmitted patients were older (median age of 73 years vs. 68 years, p < 0.001) and had a longer length of stay for initial admission (median of 4 days vs. 3 days, p < 0.001). The most significant predictors of readmission were elective admission (OR 2.00, 95%CI 1.89–2.13, p < 0.001), cancer (OR 1.91, 95%CI 1.81–2.01, p < 0.001), chronic kidney disease (OR 1.80, 95%CI 1.73–1.87, p < 0.001), previous myocardial infarction (OR 1.59, 95%CI 1.50–1.69, p < 0.001) and liver failure (OR 1.34, 95%CI 1.06–1.68, p = 0.013). Palliative care was linked to a reduced odds of readmission (OR 0.36, 95%CI 0.31–0.41, p < 0.001). Conclusions: New cardiac-related hospital readmissions within 30 days after ischemic stroke occur in 2.4% of patients, with elective admission and cancer being a strong predictor of readmissions. Full article

MicroRNA (miR: small noncoding RNA)-150 is evolutionarily conserved and is downregulated in patients with diverse forms of heart failure (HF) and in multiple mouse models of HF. Moreover, miR-150 is markedly correlated with the outcome of patients with HF. We previously reported that systemic or cardiomyocyte-derived miR-150 in mice elicited myocardial protection through the inhibition of cardiomyocyte death, without affecting neovascularization and T cell infiltration. Our mechanistic studies also showed that the protective roles of miR-150 in ischemic mouse hearts and human cardiac fibroblasts were, in part, attributed to the inhibition of fibroblast activation via the repression of multiple profibrotic genes. However, the extent to which miR-150 expression in adult myofibroblasts (MFs) modulates the response to myocardial infarction (MI) remains unknown. Here, we develop a novel 4-hydroxytamoxifen-inducible MF-specific miR-150 conditional knockout mouse model and demonstrate that the mouse line exhibits worse cardiac dysfunction after MI. Our studies further reveal that miR-150 ablation selectively in adult MFs exacerbates cardiac damage and apoptosis after chronic MI. Lastly, MF-specific miR-150 deletion in adult mice promotes the expression of proinflammatory and profibrotic genes as well as cardiac fibrosis following chronic MI. Our findings indicate a key protective role for MF-derived miR-150 in modulating post-MI responses. Full article

Background: Hepatic chemosaturation for inoperable liver tumors is a palliative treatment option with a beneficial effect on survival. However, the procedure regularly leads to circulatory failure during the filtration phase, and hemodynamic management is challenging. Our study aimed to compare two different strategies for hemodynamic management during chemosaturation to develop hypotheses for improving patient care and reducing peri-interventional morbidity. Methods: We conducted a single-center retrospective cohort study including 66 procedures of chemosaturation between May 2016 and March 2024. Procedures were divided into two groups: group 1 was managed with norepinephrine as the only vasopressor and liberal use of hydroxyethyl starch (HES). Group 2 was managed with norepinephrine and vasopressin and the preferred use of balanced crystalloids. We compared these two groups with respect to hemodynamic parameters, laboratory values, and post-interventional complications. Results: The heart rate was highest and the mean arterial pressure (MAP) was lowest during the filtration phase in both groups (p = 0.868, p = 0.270). The vasoactive inotropic score (VIS) was significantly higher in group 2 during the filtration phase (31.5 vs. 89, p < 0.001). Group 1 received significantly more HES overall (1000 mL vs. 0 mL, p < 0.001). Lactate levels at admission to the ICU were higher in group 1 (22.9 vs. 14.45 mg/dL, p = 0.041). Platelet counts were lower in group 2 from directly after chemosaturation through day 2 (p = 0.022, p = 0.001, p = 0.032). The INR differed significantly directly after chemosaturation (1.13 vs. 1.26, p = 0.015). Overall, group 1 received significantly more blood products peri-interventionally. There were two bleedings and one ischemic stroke in the overall cohort. There was no peri-interventional mortality. Conclusions: Advanced hemodynamic management ensures low peri-interventional mortality and morbidity. High-dose vasopressors, including vasopressin and the preferred use of balanced crystalloids, are sufficient to stabilize circulatory function during chemosaturation. Full article