Cardioprotective Potential of an SGLT2 Inhibitor Against Doxorubicin-Induced Heart Failure

BACKGROUND AND OBJECTIVES@#Recent studies have shown that sodium-glucose co-transporter 2 (SGLT2) inhibitors reduce the risk of heart failure (HF)-associated hospitalization and mortality in patients with diabetes. However, it is not clear whether SGLT2 inhibitors have a cardiovascular benefit in patients without diabetes. We aimed to determine whether empagliflozin (EMPA), an SGLT2 inhibitor, has a protective role in HF without diabetes.@*METHODS@#Cardiomyopathy was induced in C57BL/6J mice using intraperitoneal injection of doxorubicin (Dox). Mice with HF were fed a normal chow diet (NCD) or an NCD containing 0.03% EMPA. Then we analyzed their phenotypes and performed in vitro experiments to reveal underlying mechanisms of the EMPA's effects.@*RESULTS@#Mice fed NCD with EMPA showed improved heart function and reduced fibrosis. In vitro studies showed similar results. Phloridzin, a non-specific SGLT inhibitor, did not show any protective effect against Dox toxicity in H9C2 cells. SGLT2 inhibitor can cause increase in blood ketone levels. Beta hydroxybutyrate (βOHB), which is well known ketone body associated with SGLT2 inhibitor, showed a protective effect against Dox in H9C2 cells and in Dox-treated mice. These results suggest elevating βOHB might be a convincing mechanism for the protective effects of SGLT2 inhibitor.@*CONCLUSIONS@#SGLT2 inhibitors have a protective effect in Dox-induced HF in mice. This implied that SGLT2 inhibitor therapy could be a good treatment strategy even in HF patients without diabetes.

Cardioprotective Potential of an SGLT2 Inhibitor Against Doxorubicin-Induced Heart Failure

BACKGROUND AND OBJECTIVES: Recent studies have shown that sodium-glucose co-transporter 2 (SGLT2) inhibitors reduce the risk of heart failure (HF)-associated hospitalization and mortality in patients with diabetes. However, it is not clear whether SGLT2 inhibitors have a cardiovascular benefit in patients without diabetes. We aimed to determine whether empagliflozin (EMPA), an SGLT2 inhibitor, has a protective role in HF without diabetes. METHODS: Cardiomyopathy was induced in C57BL/6J mice using intraperitoneal injection of doxorubicin (Dox). Mice with HF were fed a normal chow diet (NCD) or an NCD containing 0.03% EMPA. Then we analyzed their phenotypes and performed in vitro experiments to reveal underlying mechanisms of the EMPA's effects. RESULTS: Mice fed NCD with EMPA showed improved heart function and reduced fibrosis. In vitro studies showed similar results. Phloridzin, a non-specific SGLT inhibitor, did not show any protective effect against Dox toxicity in H9C2 cells. SGLT2 inhibitor can cause increase in blood ketone levels. Beta hydroxybutyrate (βOHB), which is well known ketone body associated with SGLT2 inhibitor, showed a protective effect against Dox in H9C2 cells and in Dox-treated mice. These results suggest elevating βOHB might be a convincing mechanism for the protective effects of SGLT2 inhibitor. CONCLUSIONS: SGLT2 inhibitors have a protective effect in Dox-induced HF in mice. This implied that SGLT2 inhibitor therapy could be a good treatment strategy even in HF patients without diabetes.

Effects of Coronary Artery Revascularization with a Polymer-Free Biolimus A9–Coated BioFreedom Stent Versus Bypass Surgery before Noncardiac Surgery

PURPOSE: The present study aimed to evaluate the efficacy and safety of polymer-free drug-coated BioFreedom stent implantation in comparison to coronary artery bypass graft (CABG) before major noncardiac surgery. MATERIALS AND METHODS: In a multicenter registry, 55 patients required revascularization before major noncardiac surgery that should not be delayed >6 months. Of them, 27 underwent BioFreedom stent implantation and 28 underwent CABG. Primary outcomes included rate of noncardiac surgery, time from revascularization to noncardiac surgery, and occurrence of composite outcomes (all-cause death, myocardial infarction, stent thrombosis, stroke, repeat revascularization, or major bleeding). RESULTS: The rate of major noncardiac surgery was significantly higher in the BioFreedom group (92.6%) than in the CABG group (64.3%; p=0.027). Time from revascularization to noncardiac surgery was significantly shorter in the BioFreedom group (38.0 days) than in the CABG group (73.0 days; p=0.042). During the hospitalization for revascularization period, the occurrence of primary outcomes did not differ between the groups. However, the BioFreedom group showed a shorter hospitalization period and lower total treatment cost than the CABG group. During the hospital stay for noncardiac surgery, the occurrence of composite outcome was not significantly different between groups (4% vs. 0%; p>0.999): stroke occurred in only 1 case, and there were no cases of death or stent thrombosis in the BioFreedom group. CONCLUSION: This study demonstrated that BioFreedom stenting as a revascularization strategy before major noncardiac surgery might be feasible and safe in selected patients with less severe coronary artery diseases.

Additive Beneficial Effects of Valsartan Combined with Rosuvastatin in the Treatment of Hypercholesterolemic Hypertensive Patients

BACKGROUND AND OBJECTIVES: We compared the efficacy and safety of valsartan and rosuvastatin combination therapy with each treatment alone in hypercholesterolemic hypertensive patients. SUBJECTS AND METHODS: Patients who met inclusion criteria were randomized to receive 1 of the following 2-month drug regimens: valsartan 160 mg plus rosuvastatin 20 mg, valsartan 160 mg plus placebo, or rosuvastatin 20 mg plus placebo. The primary efficacy variables were change in sitting diastolic blood pressure (sitDBP) and sitting systolic blood pressure (sitSBP), and percentage change in low-density lipoprotein-cholesterol (LDL-C) in the combination, valsartan, and rosuvastatin groups. Adverse events (AEs) during the study were analyzed. RESULTS: A total of 354 patients were screened and 123 of them were finally randomized. Changes of sitDBP by least squares mean (LSM) were -11.1, -7.2, and -3.6 mm Hg, respectively, and was greater in the combination, as compared to both valsartan (p=0.02) and rosuvastatin (p<0.001). Changes of sitSBP by LSM were -13.2, -10.8, and -4.9 mm Hg, and was greater in the combination, as compared to rosuvastatin (p=0.006) and not valsartan (p=0.42). Percentage changes of LDL-C by LSM were -52, -4, and -47% in each group, and was greater in the combination, as compared to valsartan (p<0.001), similar to rosuvastatin (p=0.16). Most AEs were mild and resolved by the end of the study. CONCLUSION: Combination treatment with valsartan and rosuvastatin exhibited an additive blood pressure-lowering effect with acceptable tolerability, as compared to valsartan monotherapy. Its lipid lowering effect was similar to rosuvatatin monotherapy.

Guidelines for the prevention and management of cardiovascular disease associated with fine dust/Asian dust exposure

Epidemiological studies have demonstrated an increased risk for cardiovascular events in relation to both short- and long-term exposure to ambient particulate matter (PM). Several plausible mechanistic pathways have been described, including an enhanced propensity for arrhythmias, systemic inflammatory responses, and the chronic promotion of atherosclerosis. On the basis of this review, several new findings were reached, including the following: exposure to PM including PM <2.5 microm in diameter can trigger cardiovascular disease-related mortality; longer-term exposure (e.g., a few years) increases the risk for cardiovascular mortality; reductions in PM levels are associated with decreases in cardiovascular mortality within a period as short as a few years; and many credible pathological mechanisms have been elucidated that lend biological plausibility to these findings. It is the opinion of the writing group that the overall evidence is consistent with a causal relationship between PM exposure and cardiovascular morbidity and mortality. Finally, PM exposure is deemed a modifiable factor that contributes to cardiovascular morbidity and mortality. The purpose of this statement is to develop evidence-based practical guidelines for healthcare professionals and regulatory agencies with a comprehensive review of the literature on air pollution and cardiovascular disease and a specific focus on the clinical implications.

Erratum to: Additive Beneficial Effects of Valsartan Combined with Rosuvastatin in the Treatment of Hypercholesterolemic Hypertensive Patients

In this article, on page 230, Fig. 2A needs to be corrected.

Percutaneous Cardiopulmonary Support-Supported Percutaneous Coronary Intervention: A Single Center Experience

BACKGROUND AND OBJECTIVES: Percutaneous cardiopulmonary support (PCPS) has proven to be a valuable technique in high-risk coronary patients undergoing percutaneous coronary intervention (PCI). However, there have been few studies on PCI associated with PCPS in Korea. We summarized our experience with PCPS-supported PCI. SUBJECTS AND METHODS: We retrospectively reviewed 19 patients with PCPS-supported PCI between August 2005 and June 2009. PCPS was used as an elective procedure for 10 patients with at least two of the following conditions: left-ventricular ejection fraction <35%, target vessel(s) supplying more than 50% of the viable myocardium, high risk surgical patients, and patients who refused coronary bypass surgery. In the remaining 9 patients PCPS was used as an emergency procedure, to stabilize and even resuscitate patients with acute myocardial infarction and cardiogenic shock, in order to attempt urgent PCI. RESULTS: Among the 19 patients who were treated with PCPS-supported PCI, 11 (57.9%) survived and 8 (42.1%) patients did not. ST elevation myocardial infarction with cardiogenic shock was more prevalent in the non-survivors than in the survivors (75% vs. 27.3%, p=0.04). The elective PCPS-supported PCI was practiced more frequently in the survivors than in the non-survivors (72.7% vs. 25%, p=0.04). In the analysis of the event-free survival curve between elective and emergency procedures, there was a significant difference in the survival rate (p=0.025). Among the survivors there were more patients with multi-vessel disease, but a lower Thrombolysis in Myocardial Infarction grade in the culprit lesions was detected in the non-survivors, before PCI. Although we studied high-risk patients, there was no procedure-related mortality. CONCLUSION: Our experience suggests that PCPS may be helpful in high risk patients treated with PCI, especially in elective cases. More aggressive and larger scale studies of PCPS should follow.

A Newly Formed and Ruptured Atheromatous Plaque within Neointima after Drug-Eluting Stent Implantation: 2-Year Follow-Up Intravascular Ultrasound and Optical Coherence Tomography Studies

Late stent thrombosis (LST) which is a life threatening complication has emerged as a serious problem of drug-eluting stents (DES). Several studies have suggested that incomplete neointimal coverage of stent struts contributes to LST. Progressive atherosclerosis within the neointima is an another possible cause of LST, but this phenomenon has seldom been reported in DES. We present a case of LST following DES implantation after a period of 28 months due to ruptured atheromatous plaque, despite complete neointimal coverage of stent struts proven by optical coherence tomography.

Gender-Based Differences in the Management and Prognosis of Acute Coronary Syndrome in Korea

PURPOSE: Gender-based differences exist in the characteristics, management, and prognosis of acute coronary syndrome (ACS). However, their impact on prognosis remains unclear. We aimed to identify factors causing these differences in Koreans. MATERIALS AND METHODS: We examined 6,636 ACS patients (66.2% males) visiting 72 Korean hospitals between April-2007 and December-2008. Gender-based differences in clinical demographics, therapy, and outcomes were analyzed over 6 months. RESULTS: Women were older than men [mean (standard deviation, SD) age, 67.6 (9.8) vs. 60.6 (11.2) years; p<0.001]; had higher rates of hypertension, diabetes mellitus, and lack of exercise (p<0.001 for all); and lower rates of obesity, familial history of cardiovascular disease (CVD), and smoking (p<0.05 for all). Atypical symptoms were more common in women (20.5% vs. 15.1% in men, p<0.001), whereas myocardial infarction with ST-segment elevation was less common (17.1% vs. 27.8%, p<0.001). Mean (SD) time lapse from symptom onset to arrival at hospital was longer in women [11.44 (18.19) vs. 8.26 (14.89) hours in men, p<0.001], as was the duration of hospitalization [7.58 (7.61) vs. 7.04 (7.72) days, p=0.007]. Fewer women underwent revascularization procedures, including thrombolytic therapy, balloon angioplasty, stent implantation, and coronary artery bypass grafting (79.4% vs. 83.3% men, p<0.001). No significant differences were observed in CVD-related death, recurrent ACS, stroke, refractory angina, or rehospitalization for angina. CONCLUSION: Female ACS patients were older than male subjects and had more atypical presentation. They arrived at the hospital later than men and had longer hospital stays, but less often required revascularization therapy. However, no gender-based differences were noted in ACS-related mortality and morbidity.

Constrictive Pericarditis Accompanied by Swine-Origin Influenza A (H1N1) Infection

Swine-origin influenza A (H1N1) is caused by a new strain of the influenza virus. The disease has spread rapidly and was declared a pandemic in April, 2009. So far, however, there is a scarcity of information regarding the complications of swine influenza. A report of the disease in the winter of 2009 in the Southern Hemisphere found that the most common manifestations of influenza A virus infection are upper respiratory tract infection and pneumonia. Although there may be an association between fulminant myocarditis and Swine influenza, cardiovascular complications resulting from swine Influenza A infection are exceedingly rare. We report a case of acute constrictive pericarditis in a healthy subject infected by the swine-origin influenza A (H1N1) virus.

Normal coronary CT angiography with subsequent adverse cardiac events / 대한내과학회지

Multi-detector row coronary computed tomography (CT) angiography is an emerging noninvasive diagnostic tool for coronary artery disease. Because of the high negative predictive value of the test, coronary CT angiography is useful for ruling out significant coronary artery stenosis in patients with chest pain. Between 2003 and 2009, 2,148 (50%) of 4,337 patients who underwent coronary CT angiography had a normal coronary artery. Of the 2,148 patients, only two (0.09%) experienced cardiovascular events within three months of their index visit. One patient underwent invasive coronary angiography based on a positive exercise test result, while the second underwent invasive coronary angiography due to an episode of chest pain. Coronary angiographic examination of these two patients revealed significant luminal narrowing of the proximal left anterior descending artery; both patients underwent revascularization at the discretion of their physician.

Pulmonary Hypertension Associated with Use of Phentermine

Weight-control drugs (known as anorexigens) such as fenfluramine have been linked with pulmonary hypertension in previous reports. In our case, a 29 year old woman was admitted for shortness of breath and was diagnosed with pulmonary hypertension. Three months ago, she had been taking phentermine for five weeks. Other factors that might have contributed to the development of pulmonary hypertension were excluded. With treatment, her symptoms improved. This is the first case that can suggest a possible connection between phenermine single medication with pulmonary hypertension. Phentermine has been considered a relatively safe drug to treat obesity, and further investigation is needed to decide the safety and dosage of phentermine.