Vasiliki V. Georgiopoulou

Evaluation of Right Intraventricular Dyssynchrony by Two-Dimensional Strain Echocardiography in Patients With Pulmonary Arterial Hypertension

BACKGROUND Right ventricular (RV) function has major prognostic implications for patients with pulmonary arterial hypertension (PAH). Intraventricular dyssynchrony might play an important role in RV dysfunction in these patients. METHODS Thirty-six patients with PAH without right bundle branch block (mean age 44 +/- 14 yr, 24 women) and 39 controls (mean age 43 +/- 18 yr, 26 women) were evaluated. Global and segmental RV longitudinal deformation parameters were recorded by 2-dimensional strain echocardiography from apical 4-chamber views using a 6-segment RV model. The standard deviation of the heart rate-corrected intervals from QRS onset to peak strain for the 6 segments (RV-SD(6)) was used to quantify right intraventricular dyssynchrony. RESULTS RV-SD(6) was significantly higher in patients with PAH compared with controls (63 +/- 21 vs 25 +/- 15ms, P < .001). Dyssynchrony in patients with PAH was found to derive mainly from delayed contraction of the basal and mid RV free wall. In patients with PAH, RV-SD(6) was strongly correlated with RV fractional area change (beta = -.519, P = .002), RV myocardial performance index (beta = .427, P = .009), and RV global strain (beta = .512, P = .002); in models controlling for RV systolic pressure, RV size, and QRS duration, RV-SD(6) was still an independent predictor of RV fractional area change (beta = -.426, P = .005) and RV global strain (beta = .358, P = .031). RV function was significantly worse in the subgroup of patients with PAH (n = 25) with RV-SD(6) > 55 ms (the upper 95% limit in controls). CONCLUSION Right intraventricular dyssynchrony, as quantified by 2-dimensional strain echocardiography, is prevalent in PAH and is associated with more pronounced RV dysfunction. The clinical implications of these findings remain to be determined in follow-up studies.

Digoxin Therapy Does Not Improve Outcomes in Patients With Advanced Heart Failure on Contemporary Medical Therapy

Background—The impact of digoxin on outcomes of patients with advanced heart failure (HF) receiving optimal contemporary therapy is not known. Methods and Results—We retrospectively reviewed data of 455 advanced HF patients referred for transplant evaluation (age, 52±12 years; ejection fraction, 18.3±8%); 227 (49.9%) were on digoxin at baseline. Primary outcome was death (n=101), urgent transplantation (n=14), or ventricular assist device implantation (n=4); secondary outcomes included HF and all-cause hospitalizations. Digoxin use was evaluated (1) in the original cohort; (2) in a propensity score–matched subset (n=322); (3) as a time-dependent covariate; and (4) after adjustment for Seattle Heart Failure Score. Patients were on optimal therapy: angiotensin-II modulation, 92.5%; β-blockers, 91.2%; aldosterone antagonists, 45.6%; and devices, 71.0%. After a median of 27 months, 83 of 277 (36.6%) patients treated with digoxin versus 36 of 228 (15.8%) patients without digoxin met primary outcome (hazard ratio [HR], 2.28; 95% CI, 1.51 to 3.43; P<0.001). This risk persisted in the matched subset (HR, 1.73; 95% CI, 1.09 to 2.75; P=0.021) and with time-varying digoxin use (HR, 2.05; 95% CI, 1.23 to 3.41; P=0.011). Digoxin was associated with higher risk among patients in sinus rhythm compared with atrial fibrillation. Digoxin was not associated with improvement in either all-cause or HF hospitalization rates. These results were similar across sex and race and when adjusted for Seattle Heart Failure Score and renal function. Conclusion—This study suggests that digoxin therapy may be of no benefit in patients with advanced HF referred for cardiac transplantation who received optimal medical therapy. Treatment with digoxin should be used cautiously in such patients because of risk for adverse outcomes.

Natriuretic peptide-guided levosimendan therapy for heart failure: A promising new approach

We read with great interest the letter by Cavusoglu et al. demonstrating that in patients with acute decompensated heart failure (ADHF) levosimendan treatment leads to a significant reduction in NT-proBNP levels for at least up to 48 h [1]. These results are in concordance with previous studies [2–6]. Such a trend was not seen with dobutamine infusion. Considering the now well accepted prognostic importance of natriuretic peptide levels in patients with heart failure, it would have been of great interest if the investigators had measured the levels of NT-proBNP longitudinally over time for a longer duration to document the overall magnitude and duration of NT-proBNP suppression by a single 24-h levosimendan infusion. Moreover, a concomitant group of patients receiving only diuretic therapy would have further helped navigate the difficult and largely unanswered question of how to optimally manage patients with ADHF. Nevertheless, the investigators do provide important new insights into the neurohormonal modulation by levosimendan that raises important novel therapeutic questions. Of great interest is the fact that none of the patients were receiving treatment with a β-blocker agent prior to the administration of the study drug. Although from an ideal

Medical therapy for acute decompensated heart failure: what recent clinical trials have taught us about diuretics and vasodilators.

Diuretics and vasodilators have been the cornerstone of heart failure (HF) therapy for decades. Although not shown to reduce mortality, diuretic and vasodilator therapy remain commonplace for treating acute decompensated HF, with diuretics being the mainstay of therapy for the removal of excess fluid in all patients with HF. This article discusses results of recent trials concerning diuretic or vasodilator therapy and HF, including the Diuretic Optimization Strategies Evaluation (DOSE) trial, the Placebo-Controlled Randomized Study of the Selective A1 Adenosine Receptor Antagonist Rolofylline for Patients Hospitalized With Acute Decompensated Heart Failure and Volume Overload to Assess Treatment Effect on Congestion and Renal Function (PROTECT), and the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST), as well as results from the Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure (ASCEND-HF) trial and the Preliminary Study of Relaxin in Acute Heart Failure (Pre-RELAX-AHF).