International Journal of Cardiology

International Journal of Cardiology | Vol. 11, No. 1, January 2020 | pp. 1–8

DOI: 10.46882/2020/IJC/000130

Original Research Article

High-Dose Atorvastatin Reloading Safeguards Against Periprocedural Myocardial Infarction During Complex Percutaneous Coronary Intervention

Yusuf Demir¹, Murat Kaya¹, Ahmet Yilmaz²

¹Department of Cardiology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey

²Division of Interventional Cardiology, Hacettepe University Faculty of Medicine, Ankara, Turkey

Abstract:
Periprocedural myocardial infarction (pMI) frequently complicates complex percutaneous coronary intervention (PCI), worsening long-term outcomes. Acute statin loading reduces myonecrosis in statin-naive patients, but its cardioprotective efficacy during complex interventions in patients already receiving long-term maintenance statins requires validation. This prospective, randomized, open-label clinical trial investigated whether high-dose atorvastatin reloading before complex PCI reduces pMI in patients on chronic statin therapy. We enrolled 240 chronic statin users scheduled for complex PCI (defined as multi-vessel intervention, bifurcation lesions, or chronic total occlusions). Patients were randomized 1:1 to receive an acute reload of atorvastatin (80 mg administered 12 hours and 2 hours pre-PCI, n = 120) or to continue standard maintenance dosing alone (n = 120). The primary endpoint was the incidence of pMI, defined as an elevation of cardiac troponin I (cTnI) greater than 5 times the upper limit of normal within 24 hours post-procedure. The incidence of pMI was significantly lower in the atorvastatin reloading group than in the maintenance control group (8.3% vs. 17.5%, p = 0.03). Post-procedural mean cTnI values were also significantly lower in the reloaded cohort (0.44 ± 0.12 ng/mL vs. 0.92 ± 0.22 ng/mL, p < 0.01). No cases of acute hepatic impairment or rhabdomyolysis were reported. High-dose atorvastatin reloading safely and significantly protects against periprocedural myocardial injury during complex percutaneous coronary intervention in patients established on chronic maintenance statin therapy.

Keywords: Percutaneous coronary intervention, Atorvastatin, Statin reloading, Periprocedural myocardial infarction, Complex coronary lesions, Cardioprotection

Received: October 12, 2019; Revised: November 24, 2019; Accepted: December 15, 2019; Published: January 18, 2020

International Journal of Cardiology | Vol. 11, No. 4, April 2020 | pp. 25–32

DOI: 10.46882/2020/IJC/000133

Original Research Article

Cardioprotective Effects of Empagliflozin in a Rat Model of Diabetic Cardiomyopathy: Interplay with Mitochondrial Dynamin-Related Protein 1 Pathways

Kenji Tanaka¹, Satoshi Yamada¹, Takashi Sato²

¹Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan

²Division of Metabolic Diseases, Tokyo Medical and Dental University, Tokyo, Japan

Abstract:
Diabetic cardiomyopathy leads to progressive diastolic failure and myocardial structural derangement. Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce heart failure event rates, but their direct impact on cardiomyocyte mitochondrial dynamics remains characterized. This study investigated the protective effects of empagliflozin on myocardial remodeling and mitochondrial structural integrity in a rat model of type 2 diabetes. Type 2 diabetes was induced in adult male Wistar rats via a high-fat diet combined with a low-dose streptozotocin injection. Diabetic rats were randomized to receive either empagliflozin (10 mg/kg/day, n = 15) or vehicle control (n = 15) via oral gavage for 8 weeks. Cardiac function was monitored using tissue Doppler echocardiography, and structural mitochondrial alignment was assessed via transmission electron microscopy. Empagliflozin significantly improved the diastolic mitral inflow E/A ratio compared to the vehicle group (1.45 ± 0.12 vs. 1.05 ± 0.08, p < 0.01). Electron microscopy revealed that empagliflozin treatment prevented mitochondrial fragmentation, preserving mitochondrial aspect ratios (2.42 ± 0.15 vs. 1.54 ± 0.11, p < 0.01). Western blot analysis demonstrated that empagliflozin up-regulated the expression of mitofusin-2 (Mfn2) and down-regulated dynamin-related protein 1 (Drp1), suppressing pro-apoptotic pathways. Empagliflozin significantly improves diastolic performance and mitigates diabetic cardiomyopathy in rats by preserving mitochondrial fusion structural pathways and optimizing metabolic morphology.

Keywords: Diabetic cardiomyopathy, Empagliflozin, SGLT2 inhibitors, Mitochondrial dynamics, Mitofusin-2, Diastolic function

Received: January 08, 2020; Revised: February 22, 2020; Accepted: March 12, 2020; Published: April 18, 2020

International Journal of Cardiology | Vol. 11, No. 2, February 2020 | pp. 9–16

DOI: 10.46882/2020/IJC/000131

Original Research Article

Prognostic Value of Right Ventricular Global Longitudinal Strain in Adult Patients with Dilated Cardiomyopathy

Vasily Smirnov¹, Elena Kuzmina², Dmitry Ivanov¹

¹Department of Cardiology, Almazov National Medical Research Centre, St. Petersburg, Russia

²Division of Cardiovascular Imaging, Pavlov First Saint Petersburg State Medical University, St. Petersburg, Russia

Abstract:
While left ventricular dimensions and ejection fractions are traditionally prioritized in dilated cardiomyopathy (DCM), right ventricular (RV) performance independently impacts long-term survival. This prospective cohort study evaluated the long-term prognostic utility of right ventricular global longitudinal strain (RV-GLS) measured via two-dimensional speckle-tracking echocardiography in adult patients with DCM. We followed 185 stable DCM patients with a resting left ventricular ejection fraction (LVEF) less than 40%. Standard echocardiography quantified right ventricular fractional area change (FAC), and off-line deformation analysis measured baseline absolute RV-GLS. The primary endpoint was a composite of cardiac mortality, urgent heart transplantation, or heart failure hospitalization over a 3-year follow-up period. Over a median follow-up of 34 months, 54 patients (29.2%) reached the primary composite endpoint. An impaired absolute baseline RV-GLS (defined as less than 15.5%) was strongly associated with a higher rate of clinical events. Kaplan-Meier survival curves confirmed a significantly lower event-free survival rate in the low absolute RV-GLS cohort (log-rank p < 0.001). After adjusting for age, NYHA functional class, baseline LVEF, and serum NT-proBNP levels, multivariable Cox proportional hazards regression confirmed that an absolute RV-GLS less than 15.5% remained a potent independent predictor of long-term clinical worsening (hazard ratio: 2.14, 95% CI: 1.28–3.55, p = 0.003). Right ventricular global longitudinal strain serves as a powerful independent predictor of long-term clinical worsening in dilated cardiomyopathy, outperforming standard volumetric metrics.

Keywords: Dilated cardiomyopathy, Right ventricular function, Speckle-tracking echocardiography, Longitudinal strain, Prognosis, Heart failure worsening

Received: November 04, 2019; Revised: December 18, 2019; Accepted: January 10, 2020; Published: February 20, 2020

International Journal of Cardiology | Vol. 11, No. 10, October 2020 | pp. 73–80

DOI: 10.46882/2020/IJC/000139

Original Research Article

Efficacy of High-Dose Atorvastatin Reloading in Attenuating Periprocedural Myocardial Infarction During Complex Coronary Stenting

Yusuf Demir¹, Murat Kaya¹, Ahmet Yilmaz²

¹Department of Cardiology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey

²Division of Interventional Cardiology, Hacettepe University Faculty of Medicine, Ankara, Turkey

Abstract:
Periprocedural myocardial infarction (pMI) is a frequent complication during complex percutaneous coronary intervention (PCI). Statin reloading has shown efficacy in limiting pMI in general cohorts, but its impact during complex interventions in patients already established on maintenance statin treatment requires validation. This prospective, randomized, open-label trial evaluated whether high-dose atorvastatin reloading before complex PCI reduces pMI rates in patients on chronic statin therapy. We enrolled 240 chronic statin users undergoing complex PCI (defined as multi-vessel disease, bifurcation lesions, or total occlusions). Patients were randomized 1:1 to receive either an acute reload of atorvastatin (80 mg given 12 hours and 2 hours pre-PCI, n = 120) or to continue standard maintenance dosing (n = 120). The primary endpoint was the incidence of pMI, defined as an elevation of cardiac troponin I (cTnI) greater than 5 times the upper limit of normal within 24 hours post-procedure. The incidence of pMI was significantly lower in the atorvastatin reloading group than in the control arm (8.3% vs. 17.5%, p = 0.03). Post-procedural mean cTnI values were also significantly reduced with the reload (0.44 ± 0.12 ng/mL vs. 0.92 ± 0.22 ng/mL, p < 0.01). No cases of hepatic dysfunction or rhabdomyolysis occurred. High-dose atorvastatin reloading safely and significantly reduces periprocedural myocardial injury during complex percutaneous coronary intervention in patients on chronic maintenance statin therapy.

Keywords: Percutaneous coronary intervention, Atorvastatin, Statin reloading, Periprocedural myocardial infarction, Complex coronary lesions

Received: July 12, 2020; Revised: August 25, 2020; Accepted: September 10, 2020; Published: October 22, 2020

International Journal of Cardiology | Vol. 11, No. 6, June 2020 | pp. 41–48

DOI: 10.46882/2020/IJC/000135

Original Research Article

Three-Year Prognostic Value of Post-Procedural Moderate Paravalvular Regurgitation Following TAVI 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:
Transcatheter aortic valve implantation (TAVI) is an established alternative to surgery for high-risk patients with severe aortic stenosis. However, paravalvular regurgitation (PVR) remains a common post-procedural finding due to calcific asymmetry. This study investigated the 3-year prognostic impact of post-procedural moderate PVR on mortality and heart failure hospitalization. We prospectively followed 240 consecutive high-risk patients who underwent successful TAVI with early-generation balloon-expandable or self-expanding valves. Post-procedural PVR severity was graded using multi-parametric transthoracic echocardiography at discharge. The primary endpoint was a composite of all-cause mortality or heart failure hospitalization at 36 months. Moderate PVR was identified in 38 patients (15.8%), while 202 patients had none, trace, or mild PVR. At 3 years, the primary composite endpoint occurred significantly more frequently in the moderate PVR cohort than in the trace-to-mild group (47.4% vs. 21.8%, log-rank p < 0.001). This difference was driven by both higher all-cause mortality (28.9% vs. 12.4%, p = 0.01) and recurrent heart failure hospitalizations (36.8% vs. 14.9%, p < 0.01). Multivariable Cox proportional hazards analysis confirmed that post-procedural moderate PVR was an independent predictor of the 3-year composite endpoint (hazard ratio: 2.34, 95% CI: 1.41–3.88, p = 0.001). Post-procedural moderate paravalvular regurgitation significantly compromises 3-year survival and survival freedom from heart failure hospitalizations after TAVI, underscoring the importance of deploying next-generation anti-leak valve designs.

Keywords: Aortic stenosis, Transcatheter aortic valve implantation, Paravalvular regurgitation, Echocardiography, Mortality, Long-term outcomes

Received: March 01, 2020; Revised: April 15, 2020; Accepted: May 05, 2020; Published: June 19, 2020

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