Clinical Characteristics and Outcome of Immediate-Release Versus SLOW-Release Carvedilol in Heart Failure Patient (SLOW-HF): a Prospective Randomized, Open-Label, Multicenter Study.

PURPOSE: Carvedilol demonstrated therapeutic benefits in patients with heart failure and reduced ejection fraction (HFrEF). However, it had a short half-life time mandating twice a day administration. We investigated whether slow-release carvedilol (carvedilol-SR) is non-inferior to standard immediate-release carvedilol (carvedilol-IR) in terms of clinical efficacy in patients with HFrEF. METHODS: We randomly assigned patients with HFrEF to receive carvedilol-SR once a day or carvedilol-IR twice a day. The primary endpoint was the change in N-terminal pro B-natriuretic peptide (NT-proBNP) level from baseline to 6 months after randomization. The secondary outcomes were proportion of patients with NT-proBNP increment > 10% from baseline, mortality rate, readmission rate, changes in blood pressure, quality of life, and drug compliance. RESULTS: A total of 272 patients were randomized and treated (median follow-up time, 173 days). In each group of patients taking carvedilol-SR and those taking carvedilol-IR, clinical characteristics were well balanced. No patient died during follow-up, and there was no significant difference in the change of NT-proBNP level between two groups (-107.4 [-440.2-70.3] pg/mL vs. -91.2 [-504.1-37.4] pg/mL, p = 0.101). Change of systolic and diastolic blood pressure, control rate and response rate of blood pressure, readmission rate, and drug compliance rate were also similar. For safety outcomes, the occurrence of adverse reactions did not differ between carvedilol-SR group and carvedilol-IR group. CONCLUSION: Carvedilol-SR once a day was non-inferior to carvedilol-IR twice a day in patients with HFrEF. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03209180 (registration date: July 6, 2017).

Evaluation of a Heart Transplant Candidate.

PURPOSE OF REVIEW: Heart transplantation is the best option for irreversible and critically advanced heart failure. However, limited donor pool, the risk of rejection, infection, and right ventricular dysfunction in short-term post-transplant period, as well as, the development of coronary allograft vasculopathy and malignancy in the long-term post-transplant period limits the utility of heart transplantation for all comers with advanced heart failure. Therefore, selection of appropriate candidates is very important for the best short and long-term prognosis. In this article, we discuss the principles of selection of candidates and compare to the recently updated International Society for Heart and Lung Transplantation (ISHLT) listing criteria with the goal of updating current clinical practice. RECENT FINDINGS: We found that while most of the recommendations in the new listing criteria are continuous with the previous criteria, updated recommendations are made on the risk stratification models in choosing transplantation candidates. Recommendation on hepatic dysfunction is not directly included in the updated ISHLT listing criteria; however, adoption of the Model for End-stage Liver Disease (MELD) score and modified MELD scores in the evaluation of risk are suggested in recent studies. In conclusion, evaluation of patient selection for heart transplantation should be comprehensive and individualized with respect to indications and the risk of comorbidities of candidates. With the advancement of mechanical circulatory support (MCS), the selection of heart transplantation candidate is continuously evolving and widened. MCS as bridge to candidacy should be considered when the candidate has potentially reversible risk factors for transplantation.

Usefulness of anticoagulant therapy in the prevention of embolic complications in patients with acute infective endocarditis.

BACKGROUND: The use of anticoagulant therapy (ACT) in patients with acute infective endocarditis (IE) remains a controversial issue. Our study attempts to estimate the impact of ACT on the occurrence of embolic complications and the usefulness of ACT in the prevention of embolism in IE patients. METHODS: The present authors analyzed 150 patients with left-sided IE. Embolisms including cerebrovascular events (CVE) and the use of ACT were checked at the time of admission and during hospitalization. RESULTS: 57 patients (38.0%) experienced an embolic event. There was no significant difference in the incidence of CVE and in-hospital mortality between patients with and without warfarin use at admission, although warfarin-naïve patients were significantly more likely to have large (>1 cm) and mobile vegetation. In addition, there was no significant difference in the incidence of postadmission embolism and in-hospital death between patients with and without in-hospital ACT. On multivariate logistic regression analysis, ACT at admission was not significantly associated with a lower risk of embolism in patients with IE. CONCLUSIONS: The role of ACT in the prevention of embolism was limited in IE patients undergoing antibiotic therapy, although it seems to reduce the embolic potential of septic vegetation before treatment.

SUrvey of Guideline Adherence for Treatment of Systolic Heart Failure in Real World (SUGAR): a multi-center, retrospective, observational study.

BACKGROUND: Clinical practice guidelines have been slowly and inconsistently applied in clinical practice, and certain evidence-based, guideline-driven therapies for heart failure (HF) have been significantly underused. The purpose of this study was to survey guideline compliance and its effect on clinical outcomes in the treatment of systolic HF in Korea. METHOD AND RESULTS: The SUrvey of Guideline Adherence for Treatment of Systolic Heart Failure in Real World (SUGAR) trial was a multi-center, retrospective, observational study on subjects with systolic HF (ejection fraction <45%) admitted to 23 university hospitals. The guideline adherence indicator (GAI) was defined as a performance measure on the basis of 3 pharmacological classes: angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor II blocker (ARB), beta-blocker (BB), and aldosterone antagonist (AA). Based on the overall adherence percentage, subjects were divided into 2 groups: those with good guideline adherence (GAI ≥50%) and poor guideline adherence (GAI <50%). We included 1319 regional participants as representatives of the standard population from the Korean national census in 2008. Adherence to drugs at discharge was as follows: ACEI or ARB, 89.7%; BB, 69.2%; and AA, 65.9%. Overall, 82.7% of the patients had good guideline adherence. Overall mortality and re-hospitalization rates at 1 year were 6.2% and 37.4%, respectively. Survival analysis by log-rank test showed a significant difference in event-free survival rate of mortality (94.7% vs. 89.8%, p = 0.003) and re-hospitalization (62.3% vs. 56.4%, p = 0.041) between the good and poor guideline-adherence groups. CONCLUSIONS: Among patients with systolic HF in Korea, adherence to pharmacologic treatment guidelines as determined by performance measures, including prescription of ACEI/ARB and BB at discharge, was associated with improved clinical outcomes.

Persistent stunning induces myocardial hibernation and protection: flow/function and metabolic mechanisms.

To test the hypothesis that persistent myocardial stunning can lead to hibernating myocardium, 13 pigs were chronically instrumented, and persistent stunning was induced regionally by 6 repetitive episodes of 90-minute coronary stenosis (CS) (30% reduction in baseline coronary blood flow [CBF]) followed by full reperfusion every 12 hours. During the 1st CS, CBF fell from 43+/-2 to 31+/-2 mL/min, and anterior wall thickening (AWT) fell by 54+/-8%, but posterior WT did not change. AWT never recovered fully and remained depressed by 31+/-7% before the 6th CS, reflecting persistent myocardial stunning, but baseline CBF was not changed. Surprisingly, during the 6th CS, AWT did not fall further despite a similar reduction in CBF during CS, as occurred with the 1st episode. Regional Mo2 fell similarly during the 1st and 6th CS. During the 1st CS, plasma glucose uptake increased, whereas free fatty acid (FFA) uptake was reduced. Before the 6th CS, glucose uptake remained elevated, whereas FFA uptake remained reduced. Histology revealed enhanced glycogen deposition, which could be explained by decreased glycogen synthase kinase (GSK)-3beta protein levels and activity. These results indicate that persistent stunning, even in the absence of chronic ischemia, can recapitulate the phenotype of myocardial hibernation. This results in a shift in the flow/function relationship where a 30% decrease in CBF is no longer accompanied by a fall in myocardial function, which could be explained, in part, by a shift in substrate utilization. These hemodynamic/metabolic adjustments could facilitate survival of hibernating myocardium.

Pulmonary hemorrhage after percutaneous coronary intervention with abciximab therapy.

Abciximab has a key role in the treatment of patients with acute coronary syndromes undergoing percutaneous coronary intervention; however, an increased risk of bleeding complications is well recognized. We report a case of serious pulmonary hemorrhage after use of abciximab therapy. A definitive indication and treatment guideline should be available to minimize serious bleeding complications. Additionally, respiratory symptoms should be monitored closely for early detection of serious pulmonary hemorrhage in patients receiving abciximab therapy during percutaneous coronary intervention.