Efficacy and Safety of Dapagliflozin in Patients With Acute Heart Failure.

BACKGROUND: The primary goals during acute heart failure (AHF) hospitalization are decongestion and guideline-directed medical therapy (GDMT) optimization. Unlike diuretics or other GDMT, early dapagliflozin initiation could achieve both AHF goals. OBJECTIVES: The authors aimed to assess the diuretic efficacy and safety of early dapagliflozin initiation in AHF. METHODS: In a multicenter, open-label study, 240 patients were randomized within 24 hours of hospital presentation for hypervolemic AHF to dapagliflozin 10 mg once daily or structured usual care with protocolized diuretic titration until day 5 or hospital discharge. The primary outcome, diuretic efficiency expressed as cumulative weight change per cumulative loop diuretic dose, was compared across treatment assignment using a proportional odds model adjusted for baseline weight. Secondary and safety outcomes were adjudicated by a blinded committee. RESULTS: For diuretic efficiency, there was no difference between dapagliflozin and usual care (OR: 0.65; 95% CI: 0.41-1.02; P = 0.06). Dapagliflozin was associated with reduced loop diuretic doses (560 mg [Q1-Q3: 260-1,150 mg] vs 800 mg [Q1-Q3: 380-1,715 mg]; P = 0.006) and fewer intravenous diuretic up-titrations (P ≤ 0.05) to achieve equivalent weight loss as usual care. Early dapagliflozin initiation did not increase diabetic, renal, or cardiovascular safety events. Dapagliflozin was associated with improved median 24-hour natriuresis (P = 0.03) and urine output (P = 0.005), expediting hospital discharge over the study period. CONCLUSIONS: Early dapagliflozin during AHF hospitalization is safe and fulfills a component of GDMT optimization. Dapagliflozin was not associated with a statistically significant reduction in weight-based diuretic efficiency but was associated with evidence for enhanced diuresis among patients with AHF. (Efficacy and Safety of Dapagliflozin in Acute Heart Failure [DICTATE-AHF]; NCT04298229).

Effect of a Hospital and Postdischarge Quality Improvement Intervention on Clinical Outcomes and Quality of Care for Patients With Heart Failure With Reduced Ejection Fraction: The CONNECT-HF Randomized Clinical Trial.

Importance: Adoption of guideline-directed medical therapy for patients with heart failure is variable. Interventions to improve guideline-directed medical therapy have failed to consistently achieve target metrics, and limited data exist to inform efforts to improve heart failure quality of care. Objective: To evaluate the effect of a hospital and postdischarge quality improvement intervention compared with usual care on heart failure outcomes and care. Design, Setting, and Participants: This cluster randomized clinical trial was conducted at 161 US hospitals and included 5647 patients (2675 intervention vs 2972 usual care) followed up after a hospital discharge for acute heart failure with reduced ejection fraction (HFrEF). The trial was performed from 2017 to 2020, and the date of final follow-up was August 31, 2020. Interventions: Hospitals (n = 82) randomized to a hospital and postdischarge quality improvement intervention received regular education of clinicians by a trained group of heart failure and quality improvement experts and audit and feedback on heart failure process measures (eg, use of guideline-directed medical therapy for HFrEF) and outcomes. Hospitals (n = 79) randomized to usual care received access to a generalized heart failure education website. Main Outcomes and Measures: The coprimary outcomes were a composite of first heart failure rehospitalization or all-cause mortality and change in an opportunity-based composite score for heart failure quality (percentage of recommendations followed). Results: Among 5647 patients (mean age, 63 years; 33% women; 38% Black; 87% chronic heart failure; 49% recent heart failure hospitalization), vital status was known for 5636 (99.8%). Heart failure rehospitalization or all-cause mortality occurred in 38.6% in the intervention group vs 39.2% in usual care (adjusted hazard ratio, 0.92 [95% CI, 0.81 to 1.05). The baseline quality-of-care score was 42.1% vs 45.5%, respectively, and the change from baseline to follow-up was 2.3% vs -1.0% (difference, 3.3% [95% CI, -0.8% to 7.3%]), with no significant difference between the 2 groups in the odds of achieving a higher composite quality score at last follow-up (adjusted odds ratio, 1.06 [95% CI, 0.93 to 1.21]). Conclusions and Relevance: Among patients with HFrEF in hospitals randomized to a hospital and postdischarge quality improvement intervention vs usual care, there was no significant difference in time to first heart failure rehospitalization or death, or in change in a composite heart failure quality-of-care score. Trial Registration: ClinicalTrials.gov Identifier: NCT03035474.

Care Optimization Through Patient and Hospital Engagement Clinical Trial for Heart Failure: Rationale and design of CONNECT-HF.

Many therapies have been shown to improve outcomes for patients with heart failure (HF) in controlled settings, but there are limited data available to inform best practices for hospital and post-discharge quality improvement initiatives. The CONNECT-HF study is a prospective, cluster-randomized trial of 161 hospitals in the United States with a 2×2 factorial design. The study is designed to assess the effect of a hospital and post-discharge quality improvement intervention compared with usual care (primary objective) on HF outcomes and quality-of-care, as well as to evaluate the effect of hospitals implementing a patient-level digital intervention compared with usual care (secondary objective). The hospital and post-discharge intervention includes audit and feedback on HF clinical process measures and outcomes for patients with HF with reduced ejection fraction (HFrEF) paired with education to sites and clinicians by a trained, nationally representative group of HF and quality improvement experts. The patient-level digital intervention is an optional ancillary study and includes a mobile application and behavioral tools that are intended to facilitate improved use of guideline-directed recommendations for self-monitoring and self-management of activity and medications for HFrEF. The effects of the interventions will be measured through an opportunity-based composite score on quality and time-to-first HF readmission or death among patients with HFrEF who present to study hospitals with acute HF and who consent to participate. The CONNECT-HF study is evaluating approaches for implementing HF guideline recommendations into practice and is one of the largest HF implementation science trials performed to date.

Trends in mitral valve surgery: a single practice experience.

BACKGROUND AND AIM OF THE STUDY: Mitral repair has evolved to a point where three methods can be used to address most pathologies: full ring annuloplasty (RA) for annular disease; Gore-Tex artificial chordal replacement (ACR) for chordal disease; and autologous pericardial augmentation (PA) for leaflet disease. The study aim was to assess the impact of the increasing application of these methods on operative results over time. METHODS: Of 328 consecutive mitral valve procedures, 34% involved myxomatous prolapse, 23% rheumatic, 13% ischemic, 12% pure annular dilatation, 7% prosthetic dysfunction, 6% endocarditis, 3% hypertrophic obstructive cardiomyopathy (HOCM), and 2% 'other'. All patients underwent RA. Myxomatous prolapse was repaired with ACR, and ischemic and annular dilatation with RA alone. Rheumatic, endocarditis, and HOCM etiologies were repaired with all three methods. Patients were allocated to two-year increments, and also to repair versus replacement groups. Operative outcomes over time were assessed with linear and binomial regression. RESULTS: Overall, 66% of mitral valves were repaired; the average operative mortality was 6% (2% for repair, 7% for replacement), and 18% involved multiple valve procedures (mortality 16%). The extent of repair increased over time, from 55% to 100% of all etiologies. Over the same period, operative mortality fell from 6% in 1994 to 0% over the past six years. Other variables, such as age, presentation status, left ventricular dysfunction and etiology were relatively constant over the period. Reoperation rates after repair have been only 2% over the past 10 years of follow up. CONCLUSION: With recent innovations, most mitral disease can be repaired with combinations of RA, ACR and PA. Today, operative mortality is approaching zero, and one factor may be the increasing application of repair to all mitral pathologies. These data support the trend of expanding valve repair across most mitral disorders.

Relation between previous lipid-lowering therapy and infarct size (creatine kinase-MB level) in patients presenting with acute myocardial infarction.

Animal experimental data have shown that lipid-lowering agents reduce myocardial infarct size. This association has not been well studied in humans. We compared infarct size in 10,548 patients in the GUSTO IIb and PURSUIT trials who were (n = 1,028) or were not (n = 9,520) on lipid-lowering therapy before an enrolling myocardial infarction (MI). Patients using lipid-lowering agents before their index MI had smaller infarcts than those who were not using these agents (median peak creatine kinase [CK]-MB 4.2 vs 5.2 times the upper limit of normal [ULN]; p <0.0001). Similarly, in an unadjusted model, patients on previous lipid-lowering therapy were less likely to have a peak CK-MB >3 times the ULN (620 of 1,028 [60.3%] vs 6,486 of 9,520 patients [68.1%]; p <0.001; relative risk 0.88, 95% confidence interval 0.84 to 0.93, p <0.0001). In a covariate- and propensity-adjusted multivariable model, the association between pretreatment with lipid-lowering agents and smaller infarct size persisted (relative risk for CK-MB >3 times the ULN 0.94, 95% confidence interval 0.88 to 0.99, p = 0.04). In conclusion, patients on lipid-lowering agents before an MI had significantly smaller infarcts. These findings suggest that lipid-lowering therapy may exert additional salutary effects in the setting of acute coronary syndromes.

A new approach to mitral valve repair for rheumatic disease: preliminary study.

BACKGROUND AND AIM OF THE STUDY: The initial application of repair to rheumatic mitral disease was fraught with unacceptable recurrence rates. For this reason, rheumatic valves primarily have been replaced in recent years. Early and late outcomes with replacement, however, have continued to be suboptimal, prompting a re-examination of repair. METHODS: All eight patients encountered by the authors with rheumatic mitral valve disease over the past three years were considered for valve repair. One patient had pure stenosis, three patients had pure regurgitation, and four had advanced forms of mixed stenosis and regurgitation. Because posterior leaflet retraction was a prominent and almost uniform feature of rheumatic disease, posterior leaflet glutaraldehyde-fixed autologous pericardial gussets were placed in all cases. In the five patients with stenosis, commissural calcium was debrided, the thickened chords to the anterior leaflet were resected, extended commissurotomies performed, and an anterior leaflet 'hinge' mechanism restored. The anterior leaflet then was reattached to the base of the papillary muscles using Gore-Tex artificial chords, and all eight patients had full ring annuloplasties. RESULTS: Postoperatively, all patients had negligible gradients and no residual leak. The first patient (with mixed stenosis and regurgitation) was restudied with transesophageal echocardiography after three years, and had continued excellent valve function. There have been no intermediate-term recurrences, complications or mortalities. Operative videos and echocardiograms from these patients are available at JScottRankinMD.com. CONCLUSION: A combination of pericardial posterior leaflet gusset, anterior leaflet chordal resection/GoreTex replacement, extended commissurotomy and full ring annuloplasty allows the repair of rheumatic valves over a full range of pathologies. Early and intermediate-term results appear satisfactory. Continued aggressive application of this type of repair to rheumatic mitral disease seems to be indicated.

A new mitral valve repair strategy for hypertrophic obstructive cardiomyopathy.

BACKGROUND AND AIM OF THE STUDY: Previously, surgery hypertrophic obstructive cardiomyopathy (HOCM) has consisted primarily of septal myectomy and/or resection of the anterior mitral leaflet with low-profile valve replacement. However, recent studies have shown that the anterior papillary muscle and chordal fan can contribute to obstruction, and also that significant mitral regurgitation (MR) may be encountered. Hence, a surgical procedure was devised to address all components of this disorder. METHODS: A 37-year-old man had a history of heart murmur and NYHA class IV symptoms, despite beta-blocker therapy. Echocardiography showed severe septal hypertrophy, systolic anterior motion (SAM) of the mitral valve, severe MR and a 185 mmHg resting outflow tract gradient. At surgery, the anterior papillary muscle was found to be medially displaced and contributing to outflow obstruction. The anterior papillary muscle and chordae were resected, a 'traditional' septal myectomy was performed, and a full annuloplasty ring placed. The mitral valve was repaired by connecting the left aspect of the leaflets to the posterior papillary muscles, using Gore-Tex artificial chords. RESULTS: The patient recovered uneventfully. Interval echocardiography at one year showed a negligible outflow gradient, relief of SAM and mild residual MR. The patient currently is active, essentially asymptomatic, and not receiving any medical therapy. CONCLUSION: Previous approaches to HOCM have been limited by a small incidence of recurrent outflow gradients, pacemaker requirement, persistent MR or complications of the prosthetic valves. By comprehensively addressing all components of outflow obstruction and mitral dysfunction, this combined procedure may produce better results in certain subsets of HOCM, with the excellent late prognosis of artificial chordal replacement.