HierSpeech++: Bridging the Gap between Semantic and Acoustic Representation of Speech by Hierarchical Variational Inference for Zero-shot Speech Synthesis

Large language models (LLM)-based speech synthesis has been widely adopted in zero-shot speech synthesis. However, they require a large-scale data and possess the same limitations as previous autoregressive speech models, including slow inference speed and lack of robustness. This paper proposes HierSpeech++, a fast and strong zero-shot speech synthesizer for text-to-speech (TTS) and voice conversion (VC). We verified that hierarchical speech synthesis frameworks could significantly improve the robustness and expressiveness of the synthetic speech. Furthermore, we significantly improve the naturalness and speaker similarity of synthetic speech even in zero-shot speech synthesis scenarios. For text-to-speech, we adopt the text-to-vec framework, which generates a self-supervised speech representation and an F0 representation based on text representations and prosody prompts. Then, HierSpeech++ generates speech from the generated vector, F0, and voice prompt. We further introduce a high-efficient speech super-resolution framework from 16 kHz to 48 kHz. The experimental results demonstrated that the hierarchical variational autoencoder could be a strong zero-shot speech synthesizer given that it outperforms LLM-based and diffusion-based models. Moreover, we achieved the first human-level quality zero-shot speech synthesis. Audio samples and source code are available at https://github.com/sh-lee-prml/HierSpeechpp.Comment: 16 pages, 9 figures, 12 table

Incidence, Predictors, Treatment, and Long-Term Prognosis of Patients With Restenosis After Drug-Eluting Stent Implantation for Unprotected Left Main Coronary Artery Disease

ObjectivesThe aim of this study was to evaluate the incidence, predictors, and long-term outcomes of patients with in-stent restenosis (ISR) after percutaneous coronary intervention (PCI) with drug-eluting stents (DES) for unprotected left main coronary artery (LMCA) disease.BackgroundFew data on the clinical course and management of patients experiencing restenosis after DES treatment for unprotected LMCA disease have appeared.MethodsBetween February 2003 and November 2007, 509 consecutive patients with unprotected LMCA disease underwent DES implantation, with 402 (80.1%) undergoing routine surveillance or clinically driven angiographic follow-up. A major adverse cardiac event was defined as the composite of death, myocardial infarction (MI), or target-lesion revascularization.ResultsThe overall incidence of angiographic ISR in LMCA lesions was 17.6% (71 of 402 patients, 57 with focal-type and 14 with diffuse-type ISR. Forty patients (56.3%) underwent repeated PCI, 10 (14.1%) underwent bypass surgery, and 21 (29.6%) were treated medically. During long-term follow-up (a median of 31.7 months), there were no deaths, 1 (2.2%) MI, and 6 (9.5%) repeated target-lesion revascularization cases. The incidence of major adverse cardiac event was 14.4% in the medical group, 13.6% in the repeated PCI group, and 10.0% in the bypass surgery group (p = 0.91). Multivariate analysis showed that the occurrence of DES-ISR did not affect the risk of death or MI.ConclusionsThe incidence of ISR was 17.7% after DES stenting for LMCA. The long-term clinical prognosis of patients with DES-ISR associated with LMCA stenting might be benign, given that these patients were optimally treated with the clinical judgment of the treating physician

Stent Thrombosis, Clinical Events, and Influence of Prolonged Clopidogrel Use After Placement of Drug-Eluting Stent Data From an Observational Cohort Study of Drug-Eluting Versus Bare-Metal Stents

ObjectivesThe purpose of this study was to evaluate the risk of stent thrombosis (ST), clinical outcomes, and the benefits of extended clopidogrel use after drug-eluting stent (DES) implantation.BackgroundData are limited regarding uniform evaluation of ST and the influence of clopidogrel continuation beyond 12 months on late events after DES treatment.MethodsWe identified 7,221 patients who received DES implantation (n = 3,160) or bare-metal stent (BMS) implantation (n = 4,061), and compared long-term adverse outcomes. Additionally, 2,851 patients with DES surviving 12 months without major events were analyzed according to clopidogrel continuation.ResultsThe adjusted-risk of overall ST was similar in the 2 groups. After 1 year, however, DES patients showed a higher risk of ST; definite/probable (hazard ratio [HR]: 3.55, 95% confidence interval [CI]: 1.26 to 9.99). The adjusted-risk of death (HR: 0.60, 95% CI: 0.46 to 0.79), death/myocardial infarction (HR: 0.63, 95% CI: 0.49 to 0.81), and target lesion revascularization (HR: 0.32, 95% CI: 0.24 to 0.43) were significantly lower in the DES group than in the BMS group. Continuing clopidogrel beyond 12 months was not associated with a reduced risk for ST (HR: 0.54, 95% CI: 0.07 to 4.23), death (HR: 1.20, 95% CI: 0.55 to 2.66), or death/myocardial infarction (HR: 1.16, 95% CI: 0.56 to 2.42) after DES implantation.ConclusionsAs compared with BMS, DES showed a similar risk of overall ST, but a higher risk of very late ST. The rates of death, death/myocardial infarction, and target lesion revasuclarization were significantly lower in the DES group. Clopidogrel continuation beyond 1 year did not appear to reduce ST and clinical events after DES implantation

Long-Term Clinical Outcomes of Sirolimus- Versus Paclitaxel-Eluting Stents for Patients With Unprotected Left Main Coronary Artery Disease Analysis of the MAIN-COMPARE (Revascularization for Unprotected Left Main Coronary Artery Stenosis: Comparison of Percutaneous Coronary Angioplasty Versus Surgical Revascularization) Registry

ObjectivesThe aim of this study was to evaluate long-term clinical outcomes after implantation of sirolimus-eluting stents (SES) or paclitaxel-eluting stents (PES) among patients with unprotected left main coronary artery (LMCA) disease.BackgroundThere have been few comparisons of long-term outcomes among currently available drug-eluting stents (DES) for the treatment of LMCA disease.MethodsA total of 858 consecutive patients with unprotected LMCA stenosis were treated with SES (n = 669) or PES (n = 189) between May 2003 and June 2006. Primary outcome was the composite of death, myocardial infarction (MI), or target vessel revascularization (TVR).ResultsBaseline clinical and angiographic characteristics were similar in the 2 groups. During 3 years of follow-up, the adjusted risk of primary composite outcome was similar among the groups (SES vs. PES: 25.8% vs. 25.7%, hazard ratio [HR]: 0.95, 95% confidence interval [CI]: 0.64 to 1.41, p = 0.79). The 2 groups also showed a comparable adjusted rate of each component of outcome: death (9.1% vs. 11.0%, HR: 0.92, 95% CI: 0.47 to 1.80, p = 0.82), MI (8.1% vs. 8.0%, HR: 0.80, 95% CI: 0.43 to 1.48, p = 0.47), and TVR (12.1% vs. 10.6%, HR: 1.10, 95% CI: 0.53 to 2.29, p = 0.81). The 3-year rates of definite or probable stent thrombosis were 0.6% in the SES group and 1.6% in the PES group (adjusted p = 0.18).ConclusionsIn consecutive patients with unprotected LMCA disease undergoing DES implantation, SES and PES showed similar long-term clinical outcomes in terms of death, MI, repeat revascularization, and stent thrombosis

Complexity of Atherosclerotic Coronary Artery Disease and Long-Term Outcomes in Patients With Unprotected Left Main Disease Treated With Drug-Eluting Stents or Coronary Artery Bypass Grafting

ObjectivesThe aim of this study was to compare treatment effects of drug-eluting stents (DES) or coronary artery bypass grafting (CABG) for left main coronary artery (LMCA) disease according to the complexity of atherosclerotic disease burden.BackgroundLimited information is available on the relationships between the extent of coronary atherosclerosis and very long-term outcomes of surgical or percutaneous LMCA revascularization.MethodsA total of 1,146 patients with unprotected LMCA disease who received DES (n = 645) or underwent CABG (n = 501) were evaluated. The extent of atherosclerotic disease burden was measured using the SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) score; a low-risk score was defined as ≤22, an intermediate-risk score as 23 to 32, and a high-risk score as ≥33.ResultsAfter multivariate adjustment with the inverse-probability-of-treatment weighting method, the 5-year risks for death (6.1% for DES vs. 16.2% for CABG; hazard ratio [HR]: 0.52; 95% confidence interval [CI]: 0.21 to 1.28; p = 0.15) and the composite of death, Q-wave myocardial infarction, or stroke (6.4% vs. 16.2%; HR: 0.54; 95% CI: 0.22 to 1.34; p = 0.18) favored DES in patients with low-risk SYNTAX scores; in contrast, the 5-year risks for death (26.9% vs. 17.8%; HR: 1.46; 95% CI: 0.92 to 2.30; p = 0.11) and the composite outcome (27.6% vs. 19.5%; HR: 1.36; 95% CI: 0.87 to 2.12; p = 0.18) favored CABG in patients with high-risk SYNTAX scores (interaction p = 0.047 for death, interaction p = 0.08 for composite outcome). Patients undergoing CABG consistently had lower rates of target vessel revascularization.ConclusionsAccording to the complexity of concomitant coronary disease, there were differential treatment effects on long-term mortality in patients with unprotected LMCA disease who received DES or underwent CABG

Drug-Eluting Stenting Followed by Cilostazol Treatment Reduces Late Restenosis in Patients With Diabetes Mellitus The DECLARE-DIABETES Trial (A Randomized Comparison of Triple Antiplatelet Therapy With Dual Antiplatelet Therapy After Drug-Eluting Stent Implantation in Diabetic Patients)

ObjectivesWe sought to evaluate the impact of cilostazol on neointimal hyperplasia after drug-eluting stent (DES) implantation in patients with diabetes mellitus (DM).BackgroundAlthough cilostazol has reduced the extent of neointimal hyperplasia and restenosis in patients after bare-metal stent implantation, it is not known whether this effect occurs after DES implantation in diabetic patients.MethodsThis randomized, multicenter, prospective study compared triple antiplatelet therapy (aspirin, clopidogrel, and cilostazol, triple group, n = 200) and dual antiplatelet therapy (aspirin and clopidogrel, standard group, n = 200) for 6 months in patients with DM receiving DES. The primary end point was in-stent late loss at 6 months.ResultsThe 2 groups had similar baseline clinical and angiographic characteristics. The in-stent (0.25 ± 0.53 mm vs. 0.38 ± 0.54 mm, p = 0.025) and in-segment (0.42 ± 0.50 mm vs. 0.53 ± 0.49 mm, p = 0.031) late loss were significantly lower in the triple versus standard group, as were 6-month in-segment restenosis (8.0% vs. 15.6%, p = 0.033) and 9-month target lesion revascularization (TLR) (2.5% vs. 7.0%, p = 0.034). At 9 months, major adverse cardiac events, including death, myocardial infarction, and TLR, tended to be lower in the triple than in the standard group (3.0% vs. 7.0%, p = 0.066). Multivariate analysis showed that sirolimus-eluting stents and the use of cilostazol were strong predictors of reduced restenosis or TLR.ConclusionsTriple antiplatelet therapy after DES implantation decreased angiographic restenosis and extent of late loss, resulting in a reduced risk of 9-month TLR compared with dual antiplatelet therapy in diabetic patients

Myotonic Dystrophy Type 1 Presenting as Male Infertility

Myotonic dystrophy 1 (DM1) is a multi-system disorder characterized by endocrine defects that include testicular and tubular atrophy, oligospermia and azoospermia, and increased follicle-stimulating hormone levels. We describe a rare case of DM1 presenting as infertility in a 29-year-old man