Right heart catheterization in advanced systolic heart failure. What are the most useful haemodynamic parameters for risk stratification?

BACKGROUND: Previous studies have shown that pulmonary hypertension is a predictor of mortality in patients with systolic heart failure (SHF). Persistent pulmonary hypertension after a reactivity test is associated with a worse outcome after transplantation. Recent studies have shown the utility of different haemodynamic parameters. AIMS: To define best haemodynamic parameters for risk stratification in patients with advanced systolic heart failure. METHODS: We included 425 consecutive patients who underwent a right heart catheterization with an inotropic challenge if indicated. RESULTS: During a median (interquartile range) follow-up of 1.67 (0.49-4.49) years, there were 151 major cardiac events (126 cardiovascular deaths and 25 postoperative deaths after ventricular assist device implantation or heart transplantation). The most powerful independent predictors of major cardiac events were baseline right atrial pressure (RAP) (hazard ratio [HR]: 1.09, 95% confidence interval [CI]: 1.06-1.12; P<0.0001) and baseline pulmonary vascular resistance (PVR) (HR: 1.10; 95% CI: 1.03-1.17; P=0.002). After inotropic challenge, the only independent predictor was mean pulmonary arterial pressure (mPAP) (HR: 1.06; 95% CI: 1.03-1.09; P<0.0001). The combination of PVR (≤or>3 Wood units), RAP (30mmHg) was the best predictor of major events. CONCLUSION: We suggest using a simple algorithm based on baseline PVR, baseline RAP and mPAP after the inotropic challenge for the risk stratification of stable patients with advanced systolic heart failure.

High prevalence of arrhythmic and myocardial complications in patients with cardiac glycogenosis due to PRKAG2 mutations.

AIMS: Mutations in PRKAG2, the gene encoding for the γ2 subunit of 5'-AMP-activated protein kinase (AMPK), are responsible for an autosomal dominant glycogenosis with a cardiac presentation, associating hypertrophic cardiomyopathy (HCM), ventricular pre-excitation (VPE), and progressive heart block. The aim of this study was to perform a retrospective time-to-event study of the clinical manifestations associated with PRKAG2 mutations. METHODS AND RESULTS: A cohort of 34 patients from 9 families was recruited between 2001 and 2010. DNA were sequenced on all exons and flanking sequences of the PRKAG2 gene using Sanger sequencing. Overall, four families carried the recurrent p.Arg302Gln mutation, and the five others carried private mutations among which three had never been reported. In the total cohort, at 40 years of age, the risk of developing HCM was 61%, VPE 70%, conduction block 22%, and sudden cardiac death (SCD) 20%. The global survival at 60 years of age was 66%. Thirty-two per cent of patients (N = 10) required a device implantation (5 pacemakers and 5 defibrillators) at a median age of 66 years, and two patients required heart transplant. Only one patient presented with significant skeletal muscle symptoms. No significant differences regarding the occurrence of VPE, ablation complications, or death incidence were observed between different mutations. CONCLUSION: This study of patients with PRKAG2 mutations provides a more comprehensive view of the natural history of this disease and demonstrates a high risk of cardiac complications. Early recognition of this disease appears important to allow an appropriate management.

Sildenafil in heart transplant candidates with pulmonary hypertension.

BACKGROUND: Severe pulmonary hypertension is a usual contraindication to heart transplantation. A few studies have found that sildenafil has a favourable effect on haemodynamic variables in patients with severe left ventricular systolic dysfunction. AIM: To report our clinical experience of sildenafil in patients with left ventricular systolic dysfunction and severe pulmonary hypertension. METHODS: All patients underwent echocardiography, radionuclide angiography, a cardiopulmonary exercise test and right heart catheterization before and after treatment with sildenafil. All patients were clinically stable and were receiving maximal tolerated doses of recommended drugs. RESULTS: We included 18 patients, with a mean±standard deviation age of 47±13 years. After a median of 8.7 months (interquartile range, 4.4-13.5 months) on sildenafil, there was a significant improvement in New York Heart Association classification (P=0.02) and mean right ventricular ejection fraction (from 26±7% to 30±9%; P=0.008), with a decrease in the VE/VCO2 slope (from 52±11 to 44±11; P=0.009) and in pulmonary vascular resistance (from 5.3±1.9 Wood units to 3.3±1.8 Wood units; P=0.01). During follow-up, three patients had urgent heart transplantation, two had non-urgent transplantation and six had left ventricular assist device implantation. All patients with pulmonary vascular resistance<3 Wood units after sildenafil were alive, compared with four in the other subgroup (44% survival). CONCLUSION: In patients with pulmonary hypertension related to left ventricular systolic dysfunction, sildenafil seems to improve cardiac haemodynamics.

Long-term functional and clinical follow-up of patients with heart failure with recovered left ventricular ejection fraction after ß-blocker therapy.

BACKGROUND: Some patients with left ventricular systolic dysfunction (LVSD) have a dramatic improvement in left ventricular ejection fraction (LVEF) after ß-blockade. No study has analyzed the long-term echocardiographic and clinical follow-up of this subgroup of patients. METHODS AND RESULTS: We included in this analysis 174 consecutive patients with LVSD who had an LVEF≥45% after ß-blockade. We performed a long-term echocardiographic follow-up (median 7.7 [4-9.9] years) and clinical follow-up (median 9.2 [7.2-10.8] years). LVEF improved from 33±8% to 54±6% after ß-blockade (P<0.0001). At the last echocardiographic evaluation, 26% of the patients had an LVEF<45% (mean±SD: 34±6%), whereas 74% still had an LVEF≥45% (mean±SD: 54±6%). Independent predictors of LVEF deterioration were a low LVEF, a high left ventricular end-diastolic diameter and a low heart rate after ß-blockade, and the presence of a complete left bundle-branch block. In the overall study population, survival rates were 90% at 5 years and 75% at 10 years. Cardiovascular death rate was 9%, noncardiovascular death rate was 11%, and unknown death rate was 3%. Patients with subsequent LVEF deterioration had a higher cardiovascular mortality compared with patients with sustained recovered LVEF (22% versus 4%). CONCLUSIONS: The long-term survival of patients with LVSD and with near-normal LVEF after ß-blockade is good. However, a quarter of these patients may experience a subsequent degradation of LVEF. These patients are at higher risk of cardiovascular mortality.