Randomized Trial of Empagliflozin in Nondiabetic Patients With Heart Failure and Reduced Ejection Fraction.

BACKGROUND: Large clinical trials established the benefits of sodium-glucose cotransporter 2 inhibitors in patients with diabetes and with heart failure with reduced ejection fraction (HFrEF). The early and significant improvement in clinical outcomes is likely explained by effects beyond a reduction in hyperglycemia. OBJECTIVES: The purpose of this study was to assess the effect of empagliflozin on left ventricular (LV) function and volumes, functional capacity, and quality of life (QoL) in nondiabetic HFrEF patients. METHODS: In this double-blind, placebo-controlled trial, nondiabetic HFrEF patients (n = 84) were randomized to empagliflozin 10 mg daily or placebo for 6 months. The primary endpoint was change in LV end-diastolic and -systolic volume assessed by cardiac magnetic resonance. Secondary endpoints included changes in LV mass, LV ejection fraction, peak oxygen consumption in the cardiopulmonary exercise test, 6-min walk test, and quality of life. RESULTS: Empagliflozin was associated with a significant reduction of LV end-diastolic volume (-25.1 ± 26.0 ml vs. -1.5 ± 25.4 ml for empagliflozin vs. placebo, respectively; p < 0.001) and LV end-systolic volume (-26.6 ± 20.5 ml vs. -0.5 ± 21.9 ml for empagliflozin vs. placebo; p < 0.001). Empagliflozin was associated with reductions in LV mass (-17.8 ± 31.9 g vs. 4.1 ± 13.4 g, for empagliflozin vs. placebo, respectively; p < 0.001) and LV sphericity, and improvements in LV ejection fraction (6.0 ± 4.2 vs. -0.1 ± 3.9; p < 0.001). Patients who received empagliflozin had significant improvements in peak O2 consumption (1.1 ± 2.6 ml/min/kg vs. -0.5 ± 1.9 ml/min/kg for empagliflozin vs. placebo, respectively; p = 0.017), oxygen uptake efficiency slope (111 ± 267 vs. -145 ± 318; p < 0.001), as well as in 6-min walk test (81 ± 64 m vs. -35 ± 68 m; p < 0.001) and quality of life (Kansas City Cardiomyopathy Questionnaire-12: 21 ± 18 vs. 2 ± 15; p < 0.001). CONCLUSIONS: Empagliflozin administration to nondiabetic HFrEF patients significantly improves LV volumes, LV mass, LV systolic function, functional capacity, and quality of life when compared with placebo. Our observations strongly support a role for sodium-glucose cotransporter 2 inhibitors in the treatment of HFrEF patients independently of their glycemic status. (Are the "Cardiac Benefits" of Empagliflozin Independent of Its Hypoglycemic Activity? [ATRU-4] [EMPA-TROPISM]; NCT03485222).

Synopsis of an epidemiologic study of a Kentucky county in the Coronary Valley.

Kentucky is part of the Coronary Valley, which comprises ten states along the Ohio and Mississippi Rivers that rank among those with the highest incidence of heart disease in the United States. Kentucky consistently ranks near the highest in the nation, and within the state, the incidence is markedly higher in the eastern, Appalachian region. In a study of heart disease risk factors among residents of Clay County, which is located in this region, woe found, surprisingly, that the prevalence of elevated plasma cholesterol is slightly lower than in the United States overall. However, we noted a higher incidence of other traditional risk factors, including hypertension, cigarette smoking, obesity, and physical inactivity in this county, as well as a greater frequency of metabolic syndrome (MS) components. These findings may explain the high prevalence of cardiovascular (CV) disease in general and coronary heart disease (CHD) in particular, in parts of rural Appalachia even without the presence of significantly elevated cholesterol levels.

Mitral valve repair with Carpentier-McCarthy-Adams IMR ETlogix annuloplasty ring for ischemic mitral regurgitation: early echocardiographic results from a multi-center study.

BACKGROUND: Ischemic mitral regurgitation (IMR) is associated with asymmetric changes in annular and ventricular geometry. Surgical repair with standard symmetric annuloplasty rings results in a high incidence of residual or recurrent mitral regurgitation (MR). The Carpentier-McCarthy-Adams (CMA) IMR ETlogix annuloplasty ring is the first remodeling ring specifically designed to treat asymmetric leaflet tethering and annular dilatation. We used quantitative 2-dimensional echo to examine early results of mitral valve (MV) repair with the CMA IMR ETlogix annuloplasty ring in patients with IMR. METHODS AND RESULTS: Fifty-nine patients (aged 68+/-12 years) with grade > or = 2+ IMR (graded on a scale of 0 to 4+) underwent MV repair with the CMA IMR ETlogix annuloplasty ring. We assessed the mitral annular diameter (MAD), tethering area (TA), and tenting height (TH) of the MV in 4-chamber, 2-chamber, and long axis views at mid-systole before and 3 to 10 days after surgery. After surgery, 57 of 59 (97%) patients had grade 0 or 1+ MR, whereas 2 patients had 2+ MR. MV repair with the CMA IMR ETlogix ring significantly reduced MAD, TA, and TH (P<0.001, for all 3 echo views), particularly in the long axis and 4-chamber views. CONCLUSIONS: Surgical repair of IMR with the novel asymmetric CMA IMR ETlogix annuloplasty ring provided excellent early results with effective reduction of MR, MAD, and leaflet tethering. This novel etiology-specific strategy may result in improved outcomes in IMR patients.

Multimodal characterization of a large right atrial mass after surgical repair of an atrial septal defect.

A 43-year-old woman with exertional dyspnea and a history of surgically repaired atrial septal defect was referred for a transthoracic echocardiogram, which demonstrated a large, mobile mass in her right atrium. The mass was further characterized with contrast transesophageal echocardiography (TEE) and delayed enhancement MRI, which together suggested a thrombus, attached to the eustachian valve and prolapsing through the tricuspid valve. The mass was resected and the diagnosis confirmed on histopathologic examination. This case illustrates the utility of a multimodal approach in characterizing cardiac masses.

Echocardiography in Percutaneous Balloon Mitral Valvuloplasty.

Percutaneous balloon valvuloplasty (BV) has been used successfully in recent years for the relief of mitral stenosis, and in many instances, as an alternative to cardiac surgery. This procedure requires precise evaluation of both valve morphology and function for preprocedure decision making and follow-up of patients. Two-dimensional (2-D) echocardiography is a unique, noninvasive tool for evaluating morphologic characteristics of valve, subvalvular apparatus, and valve annular size. Doppler echocardiography provides functional information on transvalvular flow velocity, which can be used to derive pressure gradient across valve and regurgitant flow. Mitral valve area can be either obtained from 2-D echocardiography or derived from Doppler pressure half time. Echocardiography is currently the most widely used technique for assessing results of percutaneous BV. More recently, transesophageal echocardiography (TEE) has been used for the evaluation of patients undergoing percutaneous mitral BV in whom left atrial thrombus is suspected and for the intraoperative monitoring of the valvuloplasty procedure. In this article we discuss the advantages and limitations of both transthoracic echocardiography and TEE, its recent developments in monitoring the procedure, evaluation of immediate results and long term follow-up after the valvuloplasty procedure, and its clinical utility in the selection of patients for percutaneous BV.