Background: Mesenchymal stem cells (MSCs) as living biopharmaceuticals with unique properties, i.e., stemness, viability, phenotypes, paracrine activity, etc., need to be administered such that they reach the target site, maintaining these properties unchanged and are retained at the injury site to participate in the repair process. Route of delivery (RoD) remains one of the critical determinants of safety and efficacy. This study elucidates the safety and effectiveness of different RoDs of MSC treatment in heart failure (HF) based on phase II randomized clinical trials (RCTs). We hypothesize that the RoD modulates the safety and efficacy of MSC-based therapy and determines the outcome of the intervention.
Aim: To investigate the effect of RoD of MSCs on safety and efficacy in HF patients.
Methods: RCTs were retrieved from six databases. Safety endpoints included mortality and serious adverse events (SAEs), while efficacy outcomes encompassed changes in left ventricular ejection fraction (LVEF), 6-minute walk distance (6MWD), and pro-B-type natriuretic peptide (pro-BNP). Subgroup analyses on RoD were performed for all study endpoints.
Results: Twelve RCTs were included. Overall, MSC therapy demonstrated a significant decrease in mortality [relative risk (RR): 0.55, 95% confidence interval (95%CI): 0.33-0.92, P = 0.02] compared to control, while SAE outcomes showed no significant difference (RR: 0.84, 95%CI: 0.66-1.05, P = 0.11). RoD subgroup analysis revealed a significant difference in SAE among the transendocardial (TESI) injection subgroup (RR = 0.71, 95%CI: 0.54-0.95, P = 0.04). The pooled weighted mean difference (WMD) demonstrated an overall significant improvement of LVEF by 2.44% (WMD: 2.44%, 95%CI: 0.80-4.29, P value ≤ 0.001), with only intracoronary (IC) subgroup showing significant improvement (WMD: 7.26%, 95%CI: 5.61-8.92, P ≤ 0.001). Furthermore, the IC delivery route significantly improved 6MWD by 115 m (WMD = 114.99 m, 95%CI: 91.48-138.50), respectively. In biochemical efficacy outcomes, only the IC subgroup showed a significant reduction in pro-BNP by -860.64 pg/mL (WMD: -860.64 pg/Ml, 95%CI: -944.02 to -777.26, P = 0.001).
Conclusion: Our study concluded that all delivery methods of MSC-based therapy are safe. Despite the overall benefits in efficacy, the TESI and IC routes provided better outcomes than other methods. Larger-scale trials are warranted before implementing MSC-based therapy in routine clinical practice.
Background: Lipoprotein(a) [Lp(a)] is a causal risk factor for atherosclerotic cardiovascular diseases; however, its role in acute coronary syndrome (ACS) remains unclear.
Aim: To investigate the hypothesis that the Lp(a) levels are altered by various conditions during the acute phase of ACS, resulting in subsequent cardiovascular events.
Methods: From September 2009 to May 2016, 377 patients with ACS who underwent emergent coronary angiography, and 249 who completed ≥ 1000 d of follow-up were enrolled. Lp(a) levels were measured using an isoform-independent assay at each time point from before percutaneous coronary intervention (PCI) to 48 h after PCI. The primary endpoint was the occurrence of major adverse cardiac events (MACE; cardiac death, other vascular death, ACS, and non-cardiac vascular events).
Results: The mean circulating Lp(a) level decreased significantly from pre-PCI (0 h) to 12 h after (19.0 mg/dL to 17.8 mg/dL, P < 0.001), and then increased significantly up to 48 h after (19.3 mg/dL, P < 0.001). The changes from 0 to 12 h [Lp(a)Δ0-12] significantly correlated with the basal levels of creatinine [Spearman's rank correlation coefficient (SRCC): -0.181, P < 0.01] and Lp(a) (SRCC: -0.306, P < 0.05). Among the tertiles classified according to Lp(a)Δ0-12, MACE was significantly more frequent in the lowest Lp(a)Δ0-12 group than in the remaining two tertile groups (66.2% vs 53.6%, P = 0.034). A multivariate analysis revealed that Lp(a)Δ0-12 [hazard ratio (HR): 0.96, 95% confidence interval (95%CI): 0.92-0.99] and basal creatinine (HR: 1.13, 95%CI: 1.05-1.22) were independent determinants of subsequent MACE.
Conclusion: Circulating Lp(a) levels in patients with ACS decreased significantly after emergent PCI, and a greater decrease was independently associated with a worse prognosis.
Background: Inferior wall left ventricular aneurysms are rare, they develop after transmural myocardial infarction (MI) and may be associated with poorer prognosis. We present a unique case of a large aneurysm of the inferior wall complicated by ventricular tachycardia (VT) and requiring surgical resection and mitral valve replacement.
Case summary: A 59-year-old male was admitted for VT one month after he had a delayed presentation for an inferior ST-segment elevation MI and was discovered to have a large true inferior wall aneurysm on echocardiography and confirmed on coronary computed tomography (CT) angiography. Due to the sustained VT, concern for aneurysm expansion, and persistent heart failure symptoms, the patient was referred for surgical resection of the aneurysm with patch repair, mitral valve replacement, and automated implantable cardioverter defibrillator insertion with significant improvement in functional and clinical status.
Conclusion: Inferior wall aneurysms are rare and require close monitoring to identify electrical or contractile sequelae. Coronary CT angiography can outline anatomic details and guide surgical intervention to ameliorate life-threatening complications and improve performance status.
Background: The utility of D-dimer (DD) as a biomarker for acute aortic dissection (AD) is recognized. Yet, its predictive value for in-hospital mortality remains uncertain and subject to conflicting evidence.
Aim: To conduct a meta-analysis of AD-related in-hospital mortality (ADIM) with elevated DD levels.
Methods: We searched PubMed, Scopus, Embase, and Google Scholar for AD and ADIM literature through May 2022. Heterogeneity was assessed using I 2 statistics and effect size (hazard or odds ratio) analysis with random-effects models. Sample size, study type, and patients' mean age were used for subgroup analysis. The significance threshold was P < 0.05.
Results: Thirteen studies (3628 patients) were included in our study. The pooled prevalence of ADIM was 20% (95%CI: 15%-25%). Despite comparable demographic characteristics and comorbidities, elevated DD values were associated with higher ADIM risk (unadjusted effect size: 1.94, 95%CI: 1.34-2.8; adjusted effect size: 1.12, 95%CI: 1.05-1.19, P < 0.01). Studies involving patients with a mean age of < 60 years exhibited an increased mortality risk (effect size: 1.43, 95%CI: 1.23-1.67, P < 0.01), whereas no significant difference was observed in studies with a mean age > 60 years. Prospective and larger sample size studies (n > 250) demonstrated a heightened likelihood of ADIM associated with elevated DD levels (effect size: 2.57, 95%CI: 1.30-5.08, P < 0.01 vs effect size: 1.05, 95%CI: 1.00-1.11, P = 0.05, respectively).
Conclusion: Our meta-analysis shows elevated DD increases in-hospital mortality risk in AD patients, highlighting the need for larger, prospective studies to improve risk prediction models.
Perforation of the right ventricle during placement of pacing wires is a well-documented complication and can be potentially fatal. Use of temporary pacemaker, helical screw leads and steroids use prior to implant are recognised as risk factors for development of post-permanent pacemaker effusion. We reported an unusual case of pacing wire perforating interventricular septum into the left ventricle that occurred during the implant procedure performed in another institution. After the preoperative work-up and transfer to our tertiary cardiothoracic centre, the patient underwent successful surgical management. In conclusion, early recognition and timely diagnosis using advanced multimodality imaging can guide surgical intervention and prevent unfavourable consequences of device-related complications.
This editorial discusses the manuscript by Di Maria et al, published in the recent issue of the World Journal of Cardiology. We here focus on the still elusive pathophysiological mechanisms underlying cardio-renal syndrome (CRS), despite its high prevalence and the substantial worsening of both kidney function and heart failure. While the measure of right atrial pressure through right cardiac catheterization remains the most accurate albeit invasive and costly procedure, integrating bedside ultrasound into diagnostic protocols may substantially enhance the staging of venous congestion and guide therapeutic decisions. In particular, with the assessment of Doppler patterns across multiple venous districts, the Venous Excess Ultrasound (VExUS) score improves the management of fluid overload and provides insight into the underlying factors contributing to cardio-renal interactions. Integrating specific echocardiographic parameters, particularly those concerning the right heart, may thus improve the VExUS score sensitivity, offering perspective into the nuanced comprehension of cardio-renal dynamics. A multidisciplinary approach that consistently incorporates the use of ultrasound is emerging as a promising advance in the understanding and management of CRS.
Background: Infective endocarditis (IE) is a life-threatening infection with an annual mortality of 40%. Embolic events reported in up to 80% of patients. Vegetations of > 10 mm size are associated with increased embolic events and poor prognosis. There is a paucity of literature on the association of multiple vegetations with outcome.
Aim: To study the echocardiographic (ECHO) features and outcomes associated with the presence of multiple vegetations.
Methods: In this retrospective, single-center, cohort study patients diagnosed with IE were recruited from June 2017 to June 2019. A total of 84 patients were diagnosed to have IE, of whom 67 with vegetation were identified. Baseline demographic, clinical, laboratory, and ECHO parameters were reviewed. Outcomes that were studied included recurrent admission, embolic phenomenon, and mortality.
Results: Twenty-three (34%) patients were noted to have multiple vegetations, 13 (56.5%) were male and 10 (43.5%) were female. The mean age of these patients was 50. Eight (35%) had a prior episode of IE. ECHO features of moderate to severe valvular regurgitation [odds ratio (OR) = 4], presence of pacemaker lead (OR = 4.8), impaired left ventricle (LV) relaxation (OR = 4), and elevated pulmonary artery systolic pressure (PASP) (OR = 2.2) are associated with higher odds of multiple vegetations. Of these moderate to severe valvular regurgitation (P = 0.028), pacemaker lead (P = 0.039) and impaired relaxation (P = 0.028) were statistically significant. These patients were noted to have an increased association of recurrent admissions (OR = 3.6), recurrent bacteremia (OR = 2.4), embolic phenomenon (OR = 2.5), intensive care unit stay (OR = 2.8), hypotension (OR = 2.1), surgical intervention (OR = 2.8) and device removal (OR = 4.8). Of this device removal (P = 0.039) and recurrent admissions (P = 0.017) were statistically significant.
Conclusion: This study highlights the associations of ECHO predictors and outcomes in patients with IE having multiple vegetations. ECHO features of moderate to severe regurgitation, presence of pacemaker lead, impaired LV relaxation, and elevated PASP and outcomes including recurrent admissions and device removal were found to be associated with multiple vegetations.
Central venous pressure (CVP) serves as a direct approximation of right atrial pressure and is influenced by factors like total blood volume, venous compliance, cardiac output, and orthostasis. Normal CVP falls within 8-12 mmHg but varies with volume status and venous compliance. Monitoring and managing disturbances in CVP are vital in patients with circulatory shock or fluid disturbances. Elevated CVP can lead to fluid accumulation in the interstitial space, impairing venous return and reducing cardiac preload. While pulmonary artery catheterization and central venous catheter obtained measurements are considered to be more accurate, they carry risk of complications and their usage has not shown clinical improvement. Ultrasound-based assessment of the internal jugular vein (IJV) offers real-time, non-invasive measurement of static and dynamic parameters for estimating CVP. IJV parameters, including diameter and ratio, has demonstrated good correlation with CVP. Despite significant advancements in non-invasive CVP measurement, a reliable tool is yet to be found. Present methods can offer reasonable guidance in assessing CVP, provided their limitations are acknowledged.
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