International Journal of Cardiology

International Journal of Cardiology | Vol. 11, No. 8, August 2020 | pp. 57–64

DOI: 10.46882/2020/IJC/000137

Review Article

Pathophysiological Cascades, Tissue Characterization Markers, and Evolving Anti-Fibrotic Strategies in Cardiac Fibrosis

Sarah L. Jenkins¹, David M. Ross²

¹Department of Cardiovascular Sciences, British Heart Foundation Centre, King's College London, London, United Kingdom

²Division of Cardiology, Alfred Hospital, Monash University, Melbourne, Victoria, Australia

Abstract:
Cardiac fibrosis is a universal component of adverse ventricular remodeling that drives the development of arrhythmias and heart failure. This systematic review synthesizes recent molecular and clinical literature detailing the pathophysiological signaling cascades governing cardiac fibroblast activation and evaluates emerging anti-fibrotic therapeutic targets. A comprehensive literature search up to August 2014 identified 45 relevant experimental and clinical trials. Myocardial mechanical strain and localized ischemia initiate fibroblast differentiation into active myofibroblasts, a transition primarily regulated by the transforming growth factor-beta-1 (TGF-beta-1) / Smad3 pathway. Quantified clinical data indicate that excessive extracellular matrix accumulation increases ventricular stiffness, showing a pooled correlation coefficient of r = 0.74 (95% CI: 0.65–0.82) with invasive diastolic filling pressures. Emerging non-invasive imaging techniques like cardiac magnetic resonance extracellular volume (ECV) fraction mapping allow for the early quantification of diffuse interstitial fibrosis. Novel therapeutic strategies directed at silencing pro-fibrotic microRNAs (such as miR-21) or inhibiting galectin-3 signaling pathways show significant efficacy in limiting collagen volume fractions in phase II trials, achieving a pooled hazard ratio of 0.64 (95% CI: 0.44–0.92) for attenuating adverse chamber dilation. Reversing cardiac fibrosis requires an integrated approach utilizing tissue characterization markers alongside molecular inhibitors targeted at blocking the myofibroblast differentiation cascade.

Keywords: Cardiac fibrosis, Transforming growth factor-beta, Myofibroblasts, Extracellular matrix, Late gadolinium enhancement, Extracellular volume fraction

Received: May 02, 2020; Revised: June 15, 2020; Accepted: July 04, 2020; Published: August 20, 2020

International Journal of Cardiology | Vol. 10, No. 11, November 2019 | pp. 81–88

DOI: 10.46882/2019/IJC/000128

Original Research Article

Prognostic Value of Right Ventricular Longitudinal Strain in Patients Undergoing Transcatheter Aortic Valve Implantation

Jean-Pierre Dubois¹, Pierre Vigneron¹, Lucia Rossi²

¹Department of Interventional Cardiology, Hôpital Européen Georges-Pompidou, Paris, France

²Department of Cardiac Surgery, University of Milan, Milan, Italy

Abstract:
Right ventricular (RV) function is an essential modifier of outcomes in patients with severe aortic stenosis, but conventional indices like tricuspid annular plane systolic excursion (TAPSE) are limited by angle dependency. Right ventricular free-wall longitudinal strain (RV-FWS) provides a highly precise index of global RV myocardial performance. This prospective study evaluated the 2-year prognostic value of baseline RV-FWS in high-risk patients undergoing transcatheter aortic valve implantation (TAVI). We followed 180 consecutive high-risk patients who underwent successful TAVI. Transthoracic speckle-tracking echocardiography was performed within 48 hours before the procedure to quantify baseline absolute RV-FWS. The primary endpoint was a composite of all-cause mortality or heart failure rehospitalization at 24 months. Impaired baseline RV-FWS (defined as an absolute value less than 16.0%) was identified in 54 patients (30.0%). At 2 years, the primary composite endpoint occurred significantly more frequently in patients with impaired baseline RV-FWS than in those with preserved strain (44.4% vs. 21.4%, log-rank p = 0.004). This difference was driven by higher rates of heart failure rehospitalization (33.3% vs. 13.5%, p = 0.01). Multivariable Cox regression confirmed that an absolute baseline RV-FWS less than 16.0% was an independent predictor of the 2-year composite outcome (hazard ratio: 2.14, 95% CI: 1.28–3.58, p = 0.004), whereas TAPSE lost independent predictive value in the fully adjusted model. Right ventricular free-wall longitudinal strain is a powerful independent predictor of long-term mortality and heart failure rehospitalization following TAVI.

Keywords: Aortic stenosis, Transcatheter aortic valve implantation, Right ventricular function, Speckle-tracking echocardiography, Longitudinal strain, Prognosis

Received: August 04, 2019; Revised: September 15, 2019; Accepted: October 10, 2019; Published: November 18, 2019

International Journal of Cardiology | Vol. 10, No. 5, May 2019 | pp. 33–40

DOI: 10.46882/2019/IJC/000122

Original Research Article

SGLT2 Inhibition with Dapagliflozin Mitigates Myocardial Infarct Size and Attenuates Adverse Left Ventricular Remodeling in a Rat Model of Ischemia-Reperfusion Injury

Heinrich Scholz¹, Klaus Richter¹, Manfred Ziegler²

¹Department of Cardiovascular Pharmacology, University Heart Center Freiburg, Freiburg, Germany

²Division of Experimental Cardiology, Max Delbrück Center for Molecular Medicine, Berlin, Germany

Abstract:
Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce cardiovascular death and heart failure hospitalization in clinical trials, yet the localized cellular pathways driving these benefits immediately after ischemic insults remain unresolved. This study investigated the acute cardioprotective effects of dapagliflozin on myocardial infarct size and structural remodeling in a non-diabetic rat model of ischemia-reperfusion (I/R) injury. Male Sprague-Dawley rats were randomized to receive either dapagliflozin (1.5 mg/kg/day, n = 15) or vehicle control (n = 15) via oral gavage for 14 days before undergoing 30 minutes of left anterior descending coronary artery occlusion followed by 24 hours of reperfusion. Infarct size was determined using triphenyltetrazolium chloride staining, and localized inflammation was evaluated via immunohistochemistry. Pretreatment with dapagliflozin significantly limited myocardial infarct size relative to the vehicle control group (28.4% ± 3.2% vs. 44.2% ± 4.1% of the risk area, p < 0.01). Echocardiography at 24 hours revealed a preservation of left ventricular fractional shortening in the dapagliflozin cohort (28.5% ± 2.4% vs. 21.2% ± 1.9%, p < 0.05). Mechanistically, dapagliflozin-treated rats demonstrated a marked reduction in myocardial tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 expression within the border zone. Western blot analysis confirmed a significant down-regulation of cleaved caspase-3 activation alongside up-regulated AMP-activated protein kinase (AMPK) phosphorylation. Dapagliflozin exerts direct, potent cardioprotective actions against acute ischemia-reperfusion injury in non-diabetic rats by mitigating localized inflammatory cell infiltration and suppressing cardiomyocyte apoptotic cascades through active AMPK pathway modulation.

Keywords: Ischemia-reperfusion injury, Dapagliflozin, SGLT2 inhibitors, Infarct size, Apoptosis, Inflammation

Received: February 14, 2019; Revised: March 28, 2019; Accepted: April 12, 2019; Published: May 22, 2019

International Journal of Cardiology | Vol. 10, No. 12, December 2019 | pp. 89–96

DOI: 10.46882/2019/IJC/000129

Original Research Article

Independent Predictive Value of High-Sensitivity Postoperative Cardiac Troponin T Release for New-Onset Postoperative Atrial Fibrillation

Chloe Jenkins¹, Oliver Vance¹, Sarah E. Lawson²

¹Emergency Department, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia

²School of Medicine, University of Queensland, Brisbane, Queensland, Australia

Abstract:
Postoperative atrial fibrillation (POAF) is the most frequent arrhythmic complication following cardiac surgery, associated with a higher risk of systemic stroke and prolonged hospitalization. While inflammation is a recognized trigger, the role of subclinical periprocedural myocardial injury as an arrhythmogenic substrate requires verification. This prospective observational study evaluated the independent association between early postoperative high-sensitivity cardiac troponin T (hs-cTnT) elevations and the development of new-onset POAF. We enrolled 210 patients in baseline sinus rhythm who underwent elective coronary artery bypass grafting or valvular replacement surgery. Plasma hs-cTnT levels were collected preoperatively and at 12 hours post-surgery. Continuous telemetry tracked cardiac rhythms throughout the hospital stay. New-onset POAF lasting longer than 30 seconds developed in 64 patients (30.5%). Preoperative troponin levels did not differ between the cohorts. However, at 12 hours postoperatively, hs-cTnT concentrations were significantly higher in patients who subsequently developed POAF than in those who remained in sinus rhythm (425.4 ± 84.6 ng/L vs. 284.2 ± 62.1 ng/L, p < 0.001). Multivariable logistic regression revealed that a 12-hour postoperative hs-cTnT level above 350 ng/L was a potent independent predictor of POAF development (odds ratio: 2.34, 95% CI: 1.41–3.88, p = 0.002), after adjusting for surgical parameters and advanced age. Elevated early postoperative high-sensitivity cardiac troponin T release independently predicts new-onset postoperative atrial fibrillation, indicating that subclinical periprocedural myocardial injury serves as a primary driver of postoperative arrhythmogenesis.

Keywords: Atrial fibrillation, Cardiac surgery, High-sensitivity cardiac troponin T, Myocardial injury, Postoperative complications, Arrhythmogenesis

Received: September 15, 2019; Revised: October 28, 2019; Accepted: November 12, 2019; Published: December 19, 2019

International Journal of Cardiology | Vol. 10, No. 2, February 2019 | pp. 9–16

DOI: 10.46882/2019/IJC/000119

Original Research Article

Two-Dimensional Global Longitudinal Strain for Long-Term Risk Assessment in Light-Chain Cardiac Amyloidosis

Sven Lindstrom¹, Ingrid Johansson¹, Anders Nielsen²

¹Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden

²Department of Clinical Physiology, Aarhus University Hospital, Aarhus, Denmark

Abstract:
Light-chain (AL) cardiac amyloidosis is characterized by progressive extracellular amyloid fibril deposition, leading to restrictive cardiomyopathy and severe heart failure. Early recognition of myocardial involvement is essential, as conventional metrics like LVEF often remain preserved until advanced stages. This study evaluated the long-term prognostic value of speckle-tracking derived global longitudinal strain (GLS) and the relative apical sparing pattern in patients with biopsy-proven AL amyloidosis. We prospectively followed 85 patients with systemic AL amyloidosis. All patients underwent comprehensive baseline echocardiography with off-line speckle-tracking deformation imaging. The primary endpoint was all-cause mortality over a 3-year follow-up period. Myocardial involvement was defined by standard extracellular volume metrics and wall thickness. An absolute baseline GLS less than 14.5% was identified in 64.7% of the cohort. Classic apical sparing, characterized by a preserved apical strain with severely reduced basal and mid-ventricular segment deformation, was present in 52.9% of patients. Over a median follow-up of 28 months, 32 patients (37.6%) died. Kaplan-Meier survival curves showed significantly worse survival in patients with a baseline absolute GLS less than 14.5% (log-rank p < 0.001). Multivariable Cox proportional hazards regression confirmed that baseline GLS was a potent, independent predictor of 3-year all-cause mortality (hazard ratio: 1.24 per 1% absolute reduction, 95% CI: 1.11–1.38, p < 0.001), outperforming traditional biomarkers like NT-proBNP and high-sensitivity troponin T. Two-dimensional global longitudinal strain is a powerful independent predictor of mortality in light-chain cardiac amyloidosis, serving as a critical tool for early risk stratification.

Keywords: Cardiac amyloidosis, Light-chain amyloidosis, Echocardiography, Global longitudinal strain, Apical sparing, Prognosis

Received: November 08, 2013; Revised: December 20, 2013; Accepted: January 12, 2014; Published: February 22, 2019

International Journal of Cardiology | Vol. 10, No. 1, January 2019 | pp. 1–8

DOI: 10.46882/2019/IJC/000118

Original Research Article

Adjusted High-Dose Clopidogrel Maintenance Regimen in Patients with High Post-Treatment Platelet Reactivity Undergoing PCI

Ji-Hoon Kim¹, Min-Soo Park¹, Sung-Hoon Choi²

¹Department of Cardiology, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, South Korea

²Division of Electrophysiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea

Abstract:
High post-treatment platelet reactivity (HPPR) following standard clopidogrel therapy is associated with an increased risk of ischemic events after percutaneous coronary intervention (PCI). Adjusting the antiplatelet regimen based on platelet function testing could mitigate this risk. This randomized open-label trial evaluated whether a high-dose clopidogrel regimen reduces major adverse cardiovascular events (MACE) in patients with documented HPPR undergoing PCI. We screened 650 patients scheduled for elective PCI using the VerifyNow P2Y12 assay. HPPR was defined as a P2Y12 reaction unit (PRU) value greater than 230. A total of 180 patients identified with HPPR were randomized 1:1 to either the high-dose group (clopidogrel 150 mg daily, n = 90) or the standard-dose group (clopidogrel 75 mg daily, n = 90) for 6 months. The primary endpoint was a composite of cardiac death, non-fatal myocardial infarction, or definite stent thrombosis at 6 months. At 6 months, high-dose clopidogrel significantly reduced the mean PRU value from 265 ± 24 to 192 ± 31 (p < 0.001), whereas platelet reactivity remained elevated in the standard-dose group (258 ± 22 PRU). The primary composite endpoint occurred in 4.4% of the high-dose cohort compared to 12.2% of the standard-dose cohort (p = 0.04). No significant difference was observed in the incidence of TIMI major bleeding complications (2.2% vs. 1.1%, p = 0.56). Adjusting to a high-dose clopidogrel maintenance regimen in patients with verified high post-treatment platelet reactivity significantly enhances platelet inhibition and safely reduces short-term ischemic events following PCI.

Keywords: Percutaneous coronary intervention, Clopidogrel, Platelet reactivity, VerifyNow, Stent thrombosis, Antiplatelet therapy

Received: October 10, 2013; Revised: November 24, 2013; Accepted: December 15, 2013; Published: January 18, 2019