Maryse Palardy

Reduction in Mitral Regurgitation During Therapy Guided by Measured Filling Pressures in the ESCAPE Trial

Background—Dynamic mitral regurgitation (MR) contributes to decompensation in chronic dilated heart failure. Reduction of MR was the primary physiological end point in the ESCAPE trial, which compared acute therapy guided by jugular venous pressure, edema, and weight (CLIN) with therapy guided additionally by pulmonary artery catheters (PAC) toward pulmonary wedge pressure ≤15 and right atrial pressure ≤8 mm Hg. Methods and Results—Patients were randomized to PAC or CLIN during hospitalization with chronic heart failure and mean left ventricular ejection fraction 20%, and at least 1 symptom and 1 sign of congestion. MR and mitral flow patterns, measured blinded to therapy and timepoint, were available at baseline and discharge in 133 patients, and at 3 months in 104 patients. Changes in MR and related transmitral flow patterns were compared between PAC and CLIN patients. Jugular venous pressure, edema, and weights decreased similarly during therapy in the hospital for both groups. In PAC but not in CLIN patients, MR jet area, MR/left atrial area ratio, and E velocity were each significantly reduced and deceleration time increased by discharge. By 3 months, patients had clinical evidence of increased jugular venous pressure, edema, and weight since discharge, reaching significance in the PAC arm, and the change in MR was no longer different between the 2 groups, although the change in E velocity remained greater in PAC patients. Conclusions—During hospitalization, therapy guided by PAC to reduce left-sided pressures improved MR and related filling patterns more than therapy guided clinically by evidence of systemic venous congestion. This early reduction did not translate into improved outcomes out of the hospital, where volume status reverted toward baseline.

Right ventricular dysfunction during intensive pharmacologic unloading persists after mechanical unloading.

BACKGROUND Right ventricular (RV) dysfunction is associated with adverse outcomes in heart failure (HF). Mechanical unloading should be more effective than pharmacologic therapy to reduce RV afterload and improve RV function. We compared RV size and function after aggressive medical unloading therapy to that achieved in the same patients after 3 months of left ventricular assist device (LVAD) support. METHODS AND RESULTS We studied 20 patients who underwent isolated LVAD placement (9 pulsatile and 11 axial flow). Echocardiograms were performed after inpatient optimization with diuretic and inotropic therapy and compared with studies done after 3 months of LVAD support. After medical optimization right atrial pressure was 11 +/- 5 mm Hg, mean pulmonary artery pressure 36 +/- 11 mm Hg, pulmonary capillary wedge pressure 23 +/- 9 mm Hg, and cardiac index 2.0 +/- 0.6 L.min.m(2). Preoperatively, RV dysfunction was moderate (2.6 +/- 0.9 on a 0 to 4 scale), RV diameter at the base was 3.1 +/- 0.6 cm, and mid-RV was 3.5 +/- 0.6 cm. After median LVAD support of 123 days (92 to 170), RV size and global RV dysfunction (2.6 +/- 0.9) failed to improve, despite reduced RV afterload. CONCLUSIONS RV dysfunction seen on intensive medical therapy persisted after 3 months of LVAD unloading therapy. Selection of candidates for isolated LV support should anticipate persistence of RV dysfunction observed on inotropic therapy.

High early event rates in patients with questionable eligibility for advanced heart failure therapies: Results from the Medical Arm of Mechanically Assisted Circulatory Support (Medamacs) Registry

BACKGROUND The prognosis of ambulatory patients with advanced heart failure (HF) who are not yet inotrope dependent and implications for evaluation and timing for transplant or destination therapy with a left ventricular assist device (DT-LVAD) are unknown. We hypothesized that the characteristics defining eligibility for advanced HF therapies would be a primary determinant of outcomes in these patients. METHODS Ambulatory patients with advanced HF (New York Heart Association class III-IV, Interagency Registry for Mechanically Assisted Circulatory Support profiles 4-7) were enrolled across 11 centers from May 2013 to February 2015. Patients were stratified into 3 groups: likely transplant eligible, DT-LVAD eligible, and ineligible for both transplant and DT-LVAD. Clinical characteristics were collected, and patients were prospectively followed for death, transplant, and left ventricular assist device implantation. RESULTS The study enrolled 144 patients with a mean follow-up of 10 ± 6 months. Patients in the ineligible cohort (n = 43) had worse congestion, renal function, and anemia compared with transplant (n = 51) and DT-LVAD (n = 50) eligible patients. Ineligible patients had higher mortality (23.3% vs 8.0% in DT-LVAD group and 5.9% in transplant group, p = 0.02). The differences in mortality were related to lower rates of transplantation (11.8% in transplant group vs 2.0% in DT-LVAD group and 0% in ineligible group, p = 0.02) and left ventricular assist device implantation (15.7% in transplant group vs 2.0% in DT-LVAD group and 0% in ineligible group, p < 0.01). CONCLUSIONS Ambulatory patients with advanced HF who were deemed ineligible for transplant and DT-LVAD had markers of greater HF severity and a higher rate of mortality compared with patients eligible for transplant or DT-LVAD. The high early event rate in this group emphasizes the need for timely evaluation and decision making regarding lifesaving therapies.

Inhibition of the Renin-Angiotensin System and Atrial Fibrillation in Heart Failure

Background: Atrial fibrillation (AF) is the most common sustained arrhythmia encountered clinically in patients with congestive heart failure (CHF) and has been associated with increased morbidity and possibly mortality. Small retrospective studies have shown a preventive effect on AF development with the use of agents interfering with the renin-angiotensin system (RAS). Method and Results:We carried out a systematic search of the literature in the English language in order to elucidate the potential mechanism underlying this added beneficial effect of RAS inhibitors in CHF. The concepts of ionic, electrical and structural remodelling of the atrium induced by AF are discussed. Conclusion: Inhibition of RAS could prevent AF development in patients with CHF.