Bone marrow mononuclear cells (BMCs) from 20 patients with extensive reperfused myocardial infarction (MI) were used to assess their myocardial regenerative capability “in vitro” and their effect on postinfarction left ventricular (LV) remodeling. Human BMCs were labeled, seeded on top of cryoinjured mice heart slices, and cultured. BMCs showed tropism for and ability to graft into the damaged mouse cardiac tissue and, after 1 week, acquired a cardiomyocyte phenotype and expressed cardiac proteins, including connexin43. In the clinical trial, autologous BMCs (78±41×10 ⁶ per patient) were intracoronarily transplanted 13.5±5.5 days after MI. There were no adverse effects on microvascular function or myocardial injury. No major cardiac events occurred up to 11±5 months. At 6 months, magnetic resonance showed a decrease in the end-systolic volume, improvement of regional and global LV function, and increased thickness of the infarcted wall, whereas coronary restenosis was only 15%. No changes were found in a nonrandomized contemporary control group. Thus, BMCs are capable of nesting into the damaged myocardium and acquire a cardiac cell phenotype in vitro as well as safely benefiting ventricular remodeling in vivo. Large-scale randomized trials are needed now to assess the clinical efficacy of this treatment.

A polypill that includes key medications associated with improved outcomes (aspirin, angiotensin-converting–enzyme [ACE] inhibitor, and statin) has been proposed as a simple approach to the secondary prevention of cardiovascular death and complications after myocardial infarction.

Background— Percutaneous transcatheter closure of patent foramen ovale (PFO) is used as an alternative to surgery or long-term anticoagulation for the treatment of patients with paradoxical embolism and PFO. Methods and Results— We report the immediate and long-term clinical and echocardiographic outcome of 110 consecutive patients (58 males, mean age 47±14 years) who underwent transcatheter closure of PFO because of paradoxical embolism between 1995 and 2001. Procedural success, defined as successful deployment of the device and effective occlusion (no, or trivial, shunt after device placement), was achieved in all (100%) patients. There was no in-hospital mortality, 1 device migration requiring surgical intervention (0.9%), and 1 episode of cardiac tamponade (0.9%) requiring pericardiocentesis. A progressive increment in full occlusion was observed (44%, 51%, 66%, and 71% at 1 day, 6 months, and 1 and 2 years, respectively, after device placement). At a mean follow-up of 2.3 years, 2 patients experienced recurrent neurological events (1 fatal stroke and 1 transient ischemic attack), representing an annual risk of recurrence of 0.9%. In addition, 4 (3.6%) of the patients required reintervention for device malalignment or significant shunt. Kaplan-Meier analysis showed a freedom from recurrent embolic events and reintervention of 96% and 90% at 1 and 5 years, respectively. Conclusions— Transcatheter closure of PFO is a safe and effective therapy for patients with paradoxical embolism and PFO. It is associated with a high success rate, low incidence of hospital complications, and low frequency of recurrent systemic embolic events.

We aimed to determine whether treatment with sildenafil improves outcomes of patients with persistent pulmonary hypertension (PH) after correction of valvular heart disease (VHD). The sildenafil for improving outcomes after valvular correction (SIOVAC) study was a multricentric, randomized, parallel, and placebo-controlled trial that enrolled stable adults with mean pulmonary artery pressure ≥ 30 mmHg who had undergone a successful valve replacement or repair procedure at least 1 year before inclusion. We assigned 200 patients to receive sildenafil (40 mg three times daily, n = 104) or placebo (n = 96) for 6 months. The primary endpoint was the composite clinical score combining death, hospital admission for heart failure (HF), change in functional class, and patient global self-assessment. Only 27 patients receiving sildenafil improved their composite clinical score, as compared with 44 patients receiving placebo; in contrast 33 patients in the sildenafil group worsened their composite score, as compared with 14 in the placebo group [odds ratio 0.39; 95% confidence interval (CI) 0.22–0.67; P < 0.001]. The Kaplan–Meier estimates for survival without admission due to HF were 0.76 and 0.86 in the sildenafil and placebo groups, respectively (hazard ratio 2.0, 95% CI = 1.0–4.0; log-rank P = 0.044). Changes in 6-min walk test distance, natriuretic peptides, and Doppler-derived systolic pulmonary pressure were similar in both groups. Treatment with sildenafil in patients with persistent PH after successfully corrected VHD is associated to worse clinical outcomes than placebo. Off-label usage of sildenafil for treating this source of left heart disease PH should be avoided. The trial is registered with ClinicalTrials.gov, number NCT00862043.

Background — Percutaneous mitral balloon valvuloplasty (PMV) results in good immediate results, particularly in patients with echocardiographic scores (Echo-Sc) ≤8. However, which variables relate to long-term outcome is unclear. Methods and Results — We report the immediate and long-term clinical follow-up (mean, 4.2±3.7 years; range, 0.5 to 15) of 879 patients who underwent 939 PMV procedures. Patients were divided into 2 groups, Echo-Sc ≤8 (n=601) and Echo-Sc >8 (n=278). PMV resulted in an increase in mitral valve area from 1.0±0.3 to 2.0±0.6 cm ² in patients with Echo-Sc ≤8 and from 0.8±0.3 to 1.6±0.6 cm ² in patients with Echo-Sc >8 ( P <0.0001). Although adverse events (death, mitral valve surgery, and redo PMV) were low within the first 5 years of follow-up, a progressive number of events occurred beyond this period. Nevertheless, survival (82% versus 57%) and event-free survival (38% versus 22%) at 12-year follow-up was greater in patients with Echo-Sc ≤8 ( P 8, age, prior surgical commissurotomy, NYHA functional class IV, pre-PMV mitral regurgitation ≥2+, and higher post-PMV pulmonary artery pressure as independent predictors of combined events at long-term follow-up. Conclusions — The immediate and long-term outcome of patients undergoing PMV is multifactorial. The use of the Echo-Sc in conjunction with other clinical and morphological predictors of PMV outcome allows identification of patients who will obtain the best outcome from PMV.