Rationale:: CD34 ⁺ transplantation in dilated cardiomyopathy was associated with short-term improvement in left ventricular ejection fraction and exercise tolerance. Objective:: We investigated long-term effects of intracoronary CD34 ⁺ cell transplantation in dilated cardiomyopathy and the relationship between intramyocardial cell homing and clinical response. Methods and Results:: Of 110 dilated cardiomyopathy patients, 55 were randomized to receive CD34 ⁺ stem cell transplantation (SC group) and 55 received no cell therapy (controls). In the SC group, CD34 ⁺ cells were mobilized by granulocyte colony-stimulating factor and collected via apheresis. Patients underwent myocardial scintigraphy and cells were injected in the artery supplying segments with the greatest perfusion defect. At baseline, 2 groups did not differ in age, sex, left ventricular ejection fraction, or N-terminal B-type natriuretic peptide levels. At 5 years, stem cell therapy was associated with increased left ventricular ejection fraction (from 24.3 ± 6.5% to 30.0 ± 5.1%; P =0.02), increased 6-minute walk distance (from 344 ± 90 m to 477 ± 130 m; P <0.001), and decreased N-terminal B-type natriuretic peptide (from 2322 ± 1234 pg/mL to 1011 ± 893 pg/mL; P <0.01). Left ventricular ejection fraction improvement was more significant in patients with higher myocardial homing of injected cells. During follow-up, 27 (25%) patients died and 9 (8%) underwent heart transplantation. Of the 27 deaths, 13 were attributed to pump failure and 14 were attributed to sudden cardiac death. Total mortality was lower in the SC group (14%) than in controls (35%; P =0.01). The same was true of pump failure (5% vs 18%; P =0.03), but not of sudden cardiac death (9% vs 16%; P =0.39). Conclusions:: Intracoronary stem cell transplantation may be associated with improved ventricular function, exercise tolerance, and long-term survival in patients with dilated cardiomyopathy. Higher intramyocardial homing is associated with better stem cell therapy response.

Background—: In an open-label blinded study, we compared intracoronary and transendocardial CD34 ⁺ cell transplantation in patients with nonischemic dilated cardiomyopathy. Methods and Results—: Of the 40 patients with dilated cardiomyopathy, 20 were randomized to receive intracoronary injection and 20 received transendocardial CD34 ⁺ cell delivery. In both groups, CD34 ⁺ cells were mobilized by filgrastim, collected via apheresis, and labeled with technetium-99m radioisotope for single-photon emission computed tomographic imaging. In the intracoronary group, cells were injected intracoronarily in the artery supplying segments of greater perfusion defect on myocardial perfusion scintigraphy. In the transendocardial group, electroanatomic mapping was used to identify viable but dysfunctional myocardium, and transendocardial cell injections were performed. Nuclear single-photon emission computed tomographic imaging for quantification of myocardial retention was performed 18 hours thereafter. At baseline, groups did not differ in age, sex, left ventricular ejection fraction, or N-terminal pro-brain natriuretic peptide levels. The number of CD34 ⁺ cells was also comparable (105±31×10 ⁶ in the transendocardial group versus 103±27×10 ⁶ in the intracoronary group, P =0.62). At 18 hours after procedure, myocardial retention was higher in the transendocardial group (19.2±4.8%) than in the intracoronary group (4.4±1.2%, P <0.01). At 6 months, left ventricular ejection fraction improved more in the transendocardial group (+8.1±4.3%) than in the intracoronary group (+4.2±2.3%, P =0.03). The same pattern was observed for the 6-minute walk test distance (+125±33 m in the transendocardial group versus +86±13 m in the intracoronary group, P =0.03) and N-terminal pro-brain natriuretic peptide (−628±211 versus −315±133 pg/mL, P =0.04). Conclusions—: In patients with dilated cardiomyopathy, transendocardial CD34 ⁺ cell transplantation is associated with higher myocardial retention rates and greater improvement in ventricular function, N-terminal pro-brain natriuretic peptide, and exercise capacity compared with intracoronary route. Clinical Trial Registration—: URL: http://www.clinicaltrials.gov . Unique identifier: NCT01350310.

Chronic heart failure (CHF) affects over 26 million of people worldwide, and its incidence is increasing by 2% annually. Despite the significant burden that CHF poses and despite the ubiquity of sensors in our lives, methods for automatically detecting CHF are surprisingly scarce, even in the research community. We present a method for CHF detection based on heart sounds. The method combines classic Machine-Learning (ML) and end-to-end Deep Learning (DL). The classic ML learns from expert features, and the DL learns from a spectro-temporal representation of the signal. The method was evaluated on recordings from 947 subjects from six publicly available datasets and one CHF dataset that was collected for this study. Using the same evaluation method as a recent PhysoNet challenge, the proposed method achieved a score of 89.3, which is 9.1 higher than the challenge's baseline method. The method's aggregated accuracy is 92.9% (error of 7.1%); while the experimental results are not directly comparable, this error rate is relatively close to the percentage of recordings labeled as “unknown” by experts (9.7%). Finally, we identified 15 expert features that are useful for building ML models to differentiate between CHF phases (i.e., in the decompensated phase during hospitalization and in the recompensated phase) with an accuracy of 93.2%. The proposed method shows promising results both for the distinction of recordings between healthy subjects and patients and for the detection of different CHF phases. This may lead to the easier identification of new CHF patients and the development of home-based CHF monitors for avoiding hospitalizations.

Background—: We investigated the effects of transendocardial CD34 ⁺ cell transplantation in patients with ischemic cardiomyopathy. Methods and Results—: In a prospective crossover study, we enrolled 33 patients with ischemic cardiomyopathy with New York Heart Association class III and left ventricular ejection fraction <40%. In phase 1, patients were treated with medical therapy for 6 months. Thereafter, all patients underwent transendocardial CD34 ⁺ cell transplantation. Peripheral blood CD34 ⁺ cells were mobilized by granulocyte colony stimulating factor, collected via apheresis, and injected transendocardially in the areas of hibernating myocardium. Patients were followed up for 6 months after the procedure (phase 2). Two patients died during phase 1 and none during phase 2. The remaining 31 patients were 85% men, aged 57±6 years. In phase 1, we found no change in left ventricular ejection fraction (from 25.2±6.2% to 27.1±6.6%; P =0.23), N-terminal pro B-type natriuretic peptide (from 3322±3411 to 3672±5165 pg/mL; P =0.75) or 6-minute walk distance (from 373±68 to 411±116 m; P =0.17). In contrast, in phase 2 there was an improvement in left ventricular ejection fraction (from 27.1±6.6% to 34.9±10.9%; P =0.001), increase in 6-minute walk distance (from 411±116 to 496±113 m; P =0.001), and a decrease in N-terminal pro B-type natriuretic peptide (from 3672±5165 to 1488±1847 pg/mL; P =0.04). The average number of injected CD34 ⁺ cells was 90.6±7.5×10 ⁶ . Higher doses of CD34 ⁺ cells and a more diffuse distribution of transendocardial cell injections were associated with better clinical response. Conclusions—: Transendocardial CD34 ⁺ cell transplantation may be associated with improved left ventricular function, decreased N-terminal pro B-type natriuretic peptide levels, and better exercise capacity in patients with ischemic cardiomyopathy. These effects seem to be particularly pronounced in patients receiving diffusely distributed cell injections and high-dose cell therapy. Clinical Trial Registration—: URL: http://www.clinicaltrials.gov . Unique identifier: NCT01350310.