[Update on diagnostic procedures in third window syndromes. German version]. / Update zur Diagnostik der Drittfenstersyndrome.

BACKGROUND: The diagnosis of third window syndromes often poses a challenge in clinical practice. OBJECTIVE: This paper provides an up-to-date overview of diagnostic procedures in third window syndromes, with special emphasis on superior canal dehiscence syndrome (SCDS), large vestibular aqueduct syndrome (LVAS), and X-chromosomal malformation of the cochlea. MATERIALS AND METHODS: A literature search was performed in PubMed up to December 2023. Furthermore, a selection of the authors' own cases is presented. RESULTS: Audiovestibular tests for the diagnosis of third window syndromes are most often reported for patients with SCDS in the literature. In this context, cut-off values with different sensitivities and specificities have been defined for different outcome parameters of vestibular evoked myogenic potentials. Current developments include the application of electrocochleography, broadband tympanometry, video head impulse testing, and vibration-induced nystagmus. Genetic analyses are increasingly applied in LVAS. CONCLUSION: The diagnosis of third window syndromes is always based on the synthesis of patients' symptoms, clinical signs, audiovestibular test results, and imaging.

Eye movements track prioritized auditory features in selective attention to natural speech.

Over the last decades, cognitive neuroscience has identified a distributed set of brain regions that are critical for attention. Strong anatomical overlap with brain regions critical for oculomotor processes suggests a joint network for attention and eye movements. However, the role of this shared network in complex, naturalistic environments remains understudied. Here, we investigated eye movements in relation to (un)attended sentences of natural speech. Combining simultaneously recorded eye tracking and magnetoencephalographic data with temporal response functions, we show that gaze tracks attended speech, a phenomenon we termed ocular speech tracking. Ocular speech tracking even differentiates a target from a distractor in a multi-speaker context and is further related to intelligibility. Moreover, we provide evidence for its contribution to neural differences in speech processing, emphasizing the necessity to consider oculomotor activity in future research and in the interpretation of neural differences in auditory cognition.

Congestion patterns in severe tricuspid regurgitation and transcatheter treatment: Insights from a multicentre registry.

AIMS: While invasively determined congestion holds mechanistic and prognostic significance in acute heart failure (HF), its role in patients with tricuspid regurgitation (TR)-related right- heart failure (HF) undergoing transcatheter tricuspid valve intervention (TTVI) is less well established. A comprehensive understanding of congestion patterns might aid in procedural planning, risk stratification, and the identification of patients who may benefit from adjunctive therapies before undergoing TTVI. The aim of this study was to investigate the role of congestion patterns in patients with severe TR and its implications for TTVI. METHODS AND RESULTS: Within a multicentre, international TTVI registry, 813 patients underwent right heart catheterization (RHC) prior to TTVI and were followed up to 24 months. The median age was 80 (interquartile range 76-83) years and 54% were women. Both mean right atrial pressure (RAP) and pulmonary capillary wedge pressure (PCWP) were associated with 2-year mortality on Cox regression analyses with Youden index-derived cut-offs of 17 mmHg and 19 mmHg, respectively (p < 0.01 for all). However, RAP emerged as an independent predictor of outcomes following multivariable adjustments. Pre-interventionally, 42% of patients were classified as euvolaemic (RAP <17 mmHg, PCWP <19 mmHg), 23% as having left-sided congestion (RAP <17 mmHg, PCWP ≥19 mmHg), 8% as right-sided congestion (RAP ≥17 mmHg, PCWP <19 mmHg), and 27% as bilateral congestion (RAP ≥17 mmHg, PCWP ≥19 mmHg). Patients with right-sided or bilateral congestion had the lowest procedural success rates and shortest survival times. Congestion patterns allowed for discerning specific patient's physiology and specifying prognostic implications of right ventricular to pulmonary artery coupling surrogates. CONCLUSION: In this large cohort of invasively characterized patients undergoing TTVI, congestion patterns involving right-sided congestion were associated with low procedural success and higher mortality rates after TTVI. Whether pre-interventional reduction of right-sided congestion can improve outcomes after TTVI should be established in dedicated studies.

[Cochlear implantation in patients with autoimmune hearing loss]. / Cochleaimplantatversorgung bei Autoimmunschwerhörigkeit.

BACKGROUND: Autoimmune inner ear disease (AIED) manifests with recurrent fluctuating sensorineural hearing loss and vestibular symptoms. Treatment includes steroids and a variety of immunosuppressants. Despite adequate treatment, sensorineural hearing loss can be progressive to the point of deafness. In these patients, a cochlear implant (CI) is indicated. We present the case of a 25-year-old male who underwent cochlear implantation in the left ear. After implantation we noticed brisk variations in impedances which were related to application of the previously prescribed tumor necrosis alpha (TNFα) inhibitor adalimumab. OBJECTIVE: Can immunomodulatory therapy in AIED patients after CI fitting affect the quality of hearing rehabilitation? MATERIALS AND METHODS: We documented impedances and speech intelligibility (Freiburg monosyllable test) of our patient for 1 year in dependence on adalimumab therapy. RESULTS: Directly after implantation, impedances were within the normal range. During the further course, impedances started to rise, and recurrent adjustments of the implant were needed. Adalimumab therapy was reinitiated, which resulted in a subsequent reduction of impedances. CONCLUSION: Cochlear implantation can be necessary in some AIED patients and poses a sufficient method for hearing rehabilitation. Depending on the activity of the underlying disease, a rise in impedances may occur. Immunomodulatory treatment may therefore be necessary to maintain adequate hearing results with the CI.

Clinical Trajectory and Risk Stratification for Heart Failure with Preserved Ejection Fraction in a Real-World Cohort of Patients with Suspected Coronary Artery Disease.

Background: Heart failure with preserved ejection fraction (HFpEF) is a widespread condition with significant morbidity and mortality. Its clinical heterogeneity may delay the diagnosis. Aim: To identify predictors of HFpEF-related hospitalizations in ambulatory patients presenting with elevated cardiovascular risk, suspected coronary artery diseases (CADs), and positive HFpEF screenings. Methods: Consecutive patients presenting with suspected CAD, enrolled in the observational LIFE-Heart study (2006-2014, NCT00497887), and meeting HFpEF criteria per the 2016 European Society of Cardiology (ESC) guidelines were categorized according to the presence of "overlapping conditions" potentially masking or contributing to their symptoms. Additional stratification using the H2FPEF score (<2: low risk, 2-5: intermediate risk, and ≥6 high risk) was performed. Follow-up for hospitalizations, reasons of hospitalization, and death spanned a median of 6 years. Results: Of 1054 patients (66 ± 10 years, 60% male, NT-pro-BNP 286, IQR 183-574 pg/mL), 53% had overlapping conditions, while 47% had "isolated HFpEF". The H2FPEF scores classified 23%, 57%, and 20% as low-, intermediate-, and high-risk, respectively, with consistent proportions across patients with and without overlapping conditions (p = 0.91). During the follow-up observational phase, 54% were rehospitalized, 22% experienced heart failure (HF) rehospitalizations, and 11% of patients died. Multivariable logistic regression revealed a high-risk H2FPEF category as an independent predictor of HF rehospitalization in the overall cohort (odds ratio: 3.4, CI: 2.4-4.9, p < 0.01) as well as in patients with and without overlapping conditions. Furthermore, a H2FPEF score ≥ 6 was independently associated with higher mortality rates (hazard ratio: 1.8, CI: 1.2-2.6, p < 0.01) in the Cox regression analysis. Conclusions: Ambulatory patients presenting for suspected CAD and meeting HFpEF screening criteria face elevated risks for rehospitalizations over six years. Regardless of concomitant diagnoses, quantifying cardiac damage with the H2FPEF score helps in risk-stratifying patients for HF hospitalization and mortality.

Implications of tricuspid regurgitation and right ventricular volume overload in patients with heart failure with preserved ejection fraction.

AIMS: The aim of this study was to assess the pathophysiological implications of severe tricuspid regurgitation (TR) in patients with heart failure with preserved ejection fraction (HFpEF) by using tricuspid transcatheter edge-to-edge repair (T-TEER) as a model of right ventricular (RV) volume overload relief. METHODS AND RESULTS: This prospective interventional single arm trial (NCT04782908) included patients with invasively diagnosed HFpEF. The following parameters were prospectively assessed before and after T-TEER: left ventricular (LV) diastolic properties by invasive pressure-volume loop recordings; biventricular time-volume curves and function as well as septal curvature by cardiac magnetic resonance imaging; strain analyses for timing of septal motion. Overall, 20 patients (median age 78, interquartile range [IQR] 72-83 years, 65% female) were included. T-TEER reduced TR by a median of 2 (of 5) grades (IQR 2-1). T-TEER increased LV stroke volume and LV end-diastolic volume (LVEDV) (p < 0.001), without increasing LV end-diastolic pressure (LVEDP) (p = 0.094), consequently diastolic function improved with a reduction in LVEDP/LVEDV (p = 0.001) and a rightward shift of the end-diastolic pressure-volume relationship. The increase in LVEDV correlated with a decrease in RV end-diastolic volume (p < 0.001) and LV transmural pressure increased (p = 0.028). Secondary to a decrease in early RV filling, improvements in early LV filling were observed, correlating with an alleviation of leftwards bowing of the septum (p < 0.01, respectively). CONCLUSION: Diastolic LV properties in patients with HFpEF and severe TR are importantly determined by ventricular interaction in the setting of RV volume overload. T-TEER reduces RV volume overload and improves biventricular interaction and physiology.

Running on empty: Factors underpinning impaired cardiac output reserve in heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) is frequently attributed etiologically to an underlying left ventricular (LV) diastolic dysfunction, although its pathophysiology is far more complex and can exhibit significant variations among patients. This review endeavours to systematically unravel the pathophysiological heterogeneity by illustrating diverse mechanisms leading to an impaired cardiac output reserve, a central and prevalent haemodynamic abnormality in HFpEF patients. Drawing on previously published findings from our research group, we propose a pathophysiology-guided phenotyping based on the presence of: (1) LV diastolic dysfunction, (2) LV systolic pathologies, (3) arterial stiffness, (4) atrial impairment, (5) right ventricular dysfunction, (6) tricuspid valve regurgitation, and (7) chronotopic incompetence. Tailored to each specific phenotype, we explore various potential treatment options such as antifibrotic medication, diuretics, renal denervation and more. Our conclusion underscores the pivotal role of cardiac output reserve as a key haemodynamic abnormality in HFpEF, emphasizing that by phenotyping patients according to its individual pathomechanisms, insights into personalized therapeutic approaches can be gleaned.

Hearing loss, depression, and cognition in younger and older adult CI candidates.

Background and Aim: Hearing loss in old age is associated with cognitive decline and with depression. Our study aimed to investigate the relationship between hearing loss, cognitive decline, and secondary depressive symptoms in a sample of younger and older cochlear implant candidates with profound to severe hearing loss. Methods: This study is part of a larger cohort study designated to provide information on baseline data before CI. Sixty-one cochlear implant candidates with hearing loss from adulthood onwards (>18 years) were enrolled in this study. All had symmetrical sensorineural hearing loss in both ears (four-frequency hearing threshold difference of no more than 20 dB, PTA). Individuals with primary affective disorders, psychosis, below-average intelligence, poor German language skills, visual impairment, and a medical diagnosis with potential impact on cognition (e.g., neurodegenerative diseases,) were excluded. Four-frequency hearing thresholds (dB, PTA, better ear) were collected. Using the Abbreviated Profile of Hearing Aid Benefit, we assessed subjective hearing in noise. Clinical and subclinical depressive symptoms were assessed with the Beck Depression Inventory (BDI II). Cognitive status was assessed with a neurocognitive test battery. Results: Our findings revealed a significant negative association between subjective hearing in noise (APHAB subscale "Background Noise") and BDII. However, we did not observe any link between hearing thresholds, depression, and cognition. Additionally, no differences emerged between younger (25-54 years) and older subjects (55-75 years). Unexpectedly, further unplanned analyses unveiled correlations between subjective hearing in quiet environments (APHAB) and cognitive performance [phonemic fluency (Regensburg Word Fluency), cognitive flexibility (TMTB), and nonverbal episodic memory (Nonverbal Learning Test), as well as subjective hearing of aversive/loud sounds (APHAB)], cognitive performance [semantic word fluency (RWT), and inhibition (Go/Nogo) and depression]. Duration of hearing loss and speech recognition at quiet (Freiburg Monosyllables) were not related to depression and cognitive performance. Conclusion: Impact of hearing loss on mood and cognition appears to be independent, suggesting a relationship with distinct aspects of hearing loss. These results underscore the importance of considering not only conventional audiometric measures like hearing thresholds but also variables related to hearing abilities during verbal communication in everyday life, both in quiet and noisy settings.

Twenty-Four-Month Blood Pressure Results After Renal Denervation Using Endovascular Ultrasound.

BACKGROUND Renal denervation has proven its efficacy to lower blood pressure in comparison to sham treatment in recent randomized clinical trials. Although there is a large body of evidence for the durability and safety of radiofrequency-based renal denervation, there are a paucity of data for endovascular ultrasound-based renal denervation (uRDN). We aimed to assess the long-term efficacy and safety of uRDN in a single-center cohort of patients. METHODS AND RESULTS Data from 2 previous studies on uRDN were pooled. Ambulatory 24-hour blood pressure measurements were taken before as well as 3, 6, 12, and 24 months after treatment with uRDN. A total of 130 patients (mean age 63±9 years, 24% women) underwent uRDN. After 3, 6, 12, and 24 months, systolic mean 24-hour ambulatory blood pressure values were reduced by 10±12, 10±14, 8±15, and 10±15 mm Hg, respectively, when compared with baseline (P<0.001). Corresponding diastolic values were reduced by 6±8, 6±8, 5±9, and 6±9 mm Hg, respectively (P<0.001). Periprocedural adverse events occurred in 16 patients, and all recovered without sequelae. CONCLUSIONS In this single-center study, uRDN effectively lowered blood pressure up to 24 months after treatment.

Modulation of Pulsatile Left Ventricular Afterload by Renal Denervation in Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Arterial stiffening contributes to hemodynamic derangements in heart failure with preserved ejection fraction (HFpEF). We sought to investigate the impact of renal denervation on pulsatile left ventricular loading in patients with HFpEF and hypertensive patients without heart failure (control). METHODS: Patients underwent renal denervation for treatment of hypertension and were followed up at 3 months at a single center. A validated computer model of the arterial tree, noninvasive aortic flow curves, left ventricular volumes, and E/e' as inputs were used to determine key parameters of left ventricular vascular load. RESULTS: In comparison to controls (n=30), patients with HFpEF (n=30) demonstrated lower total arterial compliance (mean difference, -0.41 [95% CI, -0.72 to -0.10] mL/mm Hg), higher impedance of the proximal aorta (Zc: 0.02; 0.01 to 0.04 mHg·s/mL), premature wave reflections (shorter backward wave transit time normalized to ejection time: -3.5; -6.5% to -0.5%), and higher wave reflection magnitude (reflection coefficient: 7.3; 2.8% to 11.9%). Overall, daytime systolic (-9.2; -12.2 to -6.2 mm Hg) and diastolic blood pressures (-5.9; -7.6 to -4.1 mm Hg) as well as blood pressure variability (-2.0; -3.0 to -0.9 mm Hg) decreased after renal denervation. In patients with HFpEF, total arterial compliance (0.42; 0.17 to 0.67 mL/mm Hg) and backward transit time normalized to ejection time (1.7; 0.4% to 3.0%) increased; Zc (-0.01; -0.02 to -0.01 mm Hg·s/mL) and reflection coefficient (-2.6; -5.0% to -0.3%) decreased after renal denervation. This was accompanied by a symptomatic improvement in patients with HFpEF. CONCLUSION: HFpEF is characterized by heightened aortic stiffness and unfavorable pulsatile left ventricular load. These abnormalities are partly normalized after renal denervation.

Short-Term Effects of Different Transcatheter Edge-to-Edge Devices on Mitral Valve Geometry.

Background Short-term effects on mitral valve (MV) anatomy after transcatheter edge-to-edge repair using the PASCAL system remain unknown. Precise quantification might allow for an advanced analysis of predictors for mean transmitral gradients. Methods and Results Consecutive patients undergoing transcatheter edge-to-edge repair for secondary mitral regurgitation using PASCAL or MitraClip systems were included. Quantification of short-term MV changes throughout the cardiac cycle was performed using peri-interventional 3-dimensional MV images. Predictors for mean transmitral gradients were identified in univariable and multivariable regression analysis. Long-term results were described during 1-year follow-up. A total of 100 patients undergoing transcatheter edge-to-edge repair using PASCAL (n=50) or MitraClip systems (n=50) were included. Significant reductions of anterior-posterior diameter, annular circumference, and area throughout the cardiac cycle were found in both cohorts (P<0.05 for all). Anatomic MV orifice area remained larger in the PASCAL cohort in mid (2.8±1.0 versus 2.4±0.9 cm2; P=0.049) and late diastole (2.7±1.1 versus 2.2±0.8 cm2; P=0.036) compared with the MitraClip cohort. Besides a device-specific profile of independent predictor of mean transmitral gradients, reduction of middiastolic anatomic MV orifice area was identified as an independent predictor in both the PASCAL (ß=-0.410; P=0.001) and MitraClip cohorts (ß=-0.318; P=0.028). At follow-up, reduction of mitral regurgitation grade to mild or less was more durable in the PASCAL cohort (90% versus 72%; P=0.035). Conclusions PASCAL and MitraClip showed comparable short-term effects on MV geometry. However, PASCAL might better preserve MV function and demonstrated more durable mitral regurgitation reduction during follow-up. Identification of independent predictors for mean transmitral gradients might potentially help to guide device selection in the future.

Neural speech tracking shifts from the syllabic to the modulation rate of speech as intelligibility decreases.

The most prominent acoustic features in speech are intensity modulations, represented by the amplitude envelope of speech. Synchronization of neural activity with these modulations supports speech comprehension. As the acoustic modulation of speech is related to the production of syllables, investigations of neural speech tracking commonly do not distinguish between lower-level acoustic (envelope modulation) and higher-level linguistic (syllable rate) information. Here we manipulated speech intelligibility using noise-vocoded speech and investigated the spectral dynamics of neural speech processing, across two studies at cortical and subcortical levels of the auditory hierarchy, using magnetoencephalography. Overall, cortical regions mostly track the syllable rate, whereas subcortical regions track the acoustic envelope. Furthermore, with less intelligible speech, tracking of the modulation rate becomes more dominant. Our study highlights the importance of distinguishing between envelope modulation and syllable rate and provides novel possibilities to better understand differences between auditory processing and speech/language processing disorders.

Speech intelligibility changes the temporal evolution of neural speech tracking.

Listening to speech with poor signal quality is challenging. Neural speech tracking of degraded speech has been used to advance the understanding of how brain processes and speech intelligibility are interrelated. However, the temporal dynamics of neural speech tracking and their relation to speech intelligibility are not clear. In the present MEG study, we exploited temporal response functions (TRFs), which has been used to describe the time course of speech tracking on a gradient from intelligible to unintelligible degraded speech. In addition, we used inter-related facets of neural speech tracking (e.g., speech envelope reconstruction, speech-brain coherence, and components of broadband coherence spectra) to endorse our findings in TRFs. Our TRF analysis yielded marked temporally differential effects of vocoding: ∼50-110 ms (M50TRF), ∼175-230 ms (M200TRF), and ∼315-380 ms (M350TRF). Reduction of intelligibility went along with large increases of early peak responses M50TRF, but strongly reduced responses in M200TRF. In the late responses M350TRF, the maximum response occurred for degraded speech that was still comprehensible then declined with reduced intelligibility. Furthermore, we related the TRF components to our other neural "tracking" measures and found that M50TRF and M200TRF play a differential role in the shifting center frequency of the broadband coherence spectra. Overall, our study highlights the importance of time-resolved computation of neural speech tracking and decomposition of coherence spectra and provides a better understanding of degraded speech processing.

Fate of iatrogenic atrial septal defects following mitral transcatheter edge-to-edge repair - a subanalysis of the MITHRAS trial.

Persisting iatrogenic atrial septal defects (iASD) after transcatheter mitral edge-to-edge repair (M-TEER) are associated with impaired outcomes. We investigated the natural history of relevant iASDs with left-to-right shunting post-M-TEER, predictors of spontaneous closure of iASD between 1 and 6 months post-M-TEER, and outcomes (heart failure [HF] hospitalization) in patients with spontaneous closure versus those with persistent iASD 6 months post-M-TEER. Patients with a relevant iASD 1-month post-M-TEER, who were treated conservatively in the randomized controlled MITHRAS trial, underwent clinical follow-up including transesophageal echocardiography 6 months post-M-TEER. Overall, 36 patients (median 77 [interquartile range 65-81] years; 36% women) completed the 6-months follow-up. Six (17%) patients had a spontaneous closure of the iASD. The eccentricity index of the iASD 1-month after M-TEER was the strongest predictor for spontaneous closure (Odds ratio 3.78; 95% confidence interval 1.26-11.33, p = 0.01) and an eccentricity index of < 1.9 provided a sensitivity of 77% at a specificity of 83% for iASD persistence (Area under the curve 0.83, p < 0.001) within 6-months post M-TEER.At follow-up, a numerical difference in the endpoint of HF hospitalization between the spontaneous closure and the residual shunt group (0% vs. 20%, p = 0.25) was observed. The eccentricity of the iASD was the strongest predictor for spontaneous closure at 1-months and an eccentricity index of < 1.9 is associated with a high persistence rate for 6 month after M-TEER. Clinical Trial Registration ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT03024268 Identifier: NCT03024268. a (red) is reflecting the mayor lengthwise dimension and b (blue) the mayor oblique dimension. The eccentricity index is calculated by dividing a through b. (Open circle) is depicting an example for a round iASD and (Open rhombus) an example for an eccentric iASD 1 month after M-TEER.

Influence of linguistic properties and hearing impairment on visual speech perception skills in the German language.

Visual input is crucial for understanding speech under noisy conditions, but there are hardly any tools to assess the individual ability to lipread. With this study, we wanted to (1) investigate how linguistic characteristics of language on the one hand and hearing impairment on the other hand have an impact on lipreading abilities and (2) provide a tool to assess lipreading abilities for German speakers. 170 participants (22 prelingually deaf) completed the online assessment, which consisted of a subjective hearing impairment scale and silent videos in which different item categories (numbers, words, and sentences) were spoken. The task for our participants was to recognize the spoken stimuli just by visual inspection. We used different versions of one test and investigated the impact of item categories, word frequency in the spoken language, articulation, sentence frequency in the spoken language, sentence length, and differences between speakers on the recognition score. We found an effect of item categories, articulation, sentence frequency, and sentence length on the recognition score. With respect to hearing impairment we found that higher subjective hearing impairment is associated with higher test score. We did not find any evidence that prelingually deaf individuals show enhanced lipreading skills over people with postlingual acquired hearing impairment. However, we see an interaction with education only in the prelingual deaf, but not in the population with postlingual acquired hearing loss. This points to the fact that there are different factors contributing to enhanced lipreading abilities depending on the onset of hearing impairment (prelingual vs. postlingual). Overall, lipreading skills vary strongly in the general population independent of hearing impairment. Based on our findings we constructed a new and efficient lipreading assessment tool (SaLT) that can be used to test behavioral lipreading abilities in the German speaking population.

Multicenter Experience With the Transcatheter Leaflet Repair System for Symptomatic Tricuspid Regurgitation.

BACKGROUND: Transcatheter treatment techniques for tricuspid regurgitation (TR) have evolved in recent years, with leaflet repair being the most commonly used, but thus far evidence on the PASCAL and PASCAL Ace system is based mainly on compassionate use data. OBJECTIVES: This is the first report on commercial use in a multicenter study with a large patient cohort investigating the safety and efficacy of the PASCAL and PASCAL Ace system in the treatment of TR. METHODS: In a retrospective, multicenter, observational setting, data from all consecutive patients undergoing leaflet repair for TR at 8 centers was collected, including a centralized analysis of echocardiographic data. RESULTS: A total of 235 high-risk patients (mean age 78 ± 8 years, 49% women, mean Society of Thoracic Surgeons Predicted Risk of Mortality score 8.6% ± 6.8%) were included. TR was functional in 87% of patients and graded severe or higher in 91%. TR was successfully reduced to moderate or less in 78% of patients (P < 0.001). Procedural success was 78% (n = 153). At the latest available follow-up (median 173 days), TR reduction was sustained (78% with TR moderate or less; P < 0.001), and echocardiography showed indications of right ventricular remodeling (mean right ventricular end-diastolic diameter 56 ± 9 mm vs 53 ± 9 mm; P < 0.001). Patients' symptoms diminished significantly (63% were in New York Heart Association functional class I or II at follow-up; P < 0.001). In a device-specific analysis, the PASCAL and PASCAL Ace showed no difference in TR reduction (postprocedural TR moderate or less in 77% vs 78%; P = 0.82). CONCLUSIONS: In early clinical experience, the PASCAL (Ace) leaflet repair system has high technical and procedural success rates with efficient TR reduction and significant clinical and echocardiographic improvement at follow-up.

Characteristics of Heart Failure With Preserved Ejection Fraction Across the Range of Left Ventricular Ejection Fraction.

BACKGROUND: Recent trial data suggest that stratification of patients with heart failure with preserved ejection fraction (HFpEF) according to left ventricular ejection fraction (LVEF) provides a means for dissecting different treatment responses. However, the differential pathophysiologic considerations have rarely been described. METHODS: This prospective, single-center study analyzed consecutive symptomatic patients with HFpEF diagnosed according to the 2016 European Society of Cardiology heart failure guidelines. Patients were grouped into LVEF 50% to 60% and LVEF >60% cohorts. All patients underwent cardiac magnetic resonance imaging. Transfemoral cardiac catheterization was performed to derive load-dependent and load-independent left ventricular (LV) properties on pressure-volume loop analyses. RESULTS: Fifty-six patients with HFpEF were enrolled and divided into LVEF 50% to 60% (n=21) and LVEF >60% (n=35) cohorts. On cardiac magnetic resonance imaging, the LVEF >60% cohort showed lower LV end-diastolic volumes (P=0.019) and end-systolic volumes (P=0.001) than the LVEF 50% to 60% cohort; stroke volume (P=0.821) did not differ between the cohorts. Extracellular volume fraction was higher in the LVEF 50% to 60% cohort than in the LVEF >60% cohort (0.332 versus 0.309; P=0.018). Pressure-volume loop analyses demonstrated higher baseline LV contractility (end-systolic elastance, 1.85 vs 1.33 mm Hg/mL; P<0.001) and passive diastolic stiffness (ß constant, 0.032 versus 0.018; P=0.004) in the LVEF >60% cohort. Ventriculo-arterial coupling (end-systolic elastance/arterial elastance) at rest was in the range of optimized stroke work in the LVEF >60% cohort but was impaired in the LVEF 50% to 60% cohort (1.01 versus 0.80; P=0.005). During handgrip exercise, patients with LVEF >60% had higher increases in end-systolic elastance (1.85 versus 0.82 mm Hg/mL; P=0.023), attenuated increases in indexed end-systolic volume (-1 versus 7 mL/m²; P<0.004), and more exaggerated increases in LV filling pressures (8 vs 5 mm Hg; P=0.023). LV stroke volume decreased in the LVEF >60% cohort (P=0.007) under exertion. CONCLUSIONS: Patients with HFpEF in whom LVEF ranged from 50% to 60% demonstrated reduced contractility, impaired ventriculo-arterial coupling, and higher extracellular volume fraction. In contrast, patients with HFpEF and a LVEF >60% demonstrated a hypercontractile state with excessive LV afterload and diminished preload reserve. A LVEF-based stratification of patients with HFpEF identified distinct morphologic and pathophysiologic subphenotypes.

Cortical tracking of formant modulations derived from silently presented lip movements and its decline with age.

The integration of visual and auditory cues is crucial for successful processing of speech, especially under adverse conditions. Recent reports have shown that when participants watch muted videos of speakers, the phonological information about the acoustic speech envelope, which is associated with but independent from the speakers' lip movements, is tracked by the visual cortex. However, the speech signal also carries richer acoustic details, for example, about the fundamental frequency and the resonant frequencies, whose visuophonological transformation could aid speech processing. Here, we investigated the neural basis of the visuo-phonological transformation processes of these more fine-grained acoustic details and assessed how they change as a function of age. We recorded whole-head magnetoencephalographic (MEG) data while the participants watched silent normal (i.e., natural) and reversed videos of a speaker and paid attention to their lip movements. We found that the visual cortex is able to track the unheard natural modulations of resonant frequencies (or formants) and the pitch (or fundamental frequency) linked to lip movements. Importantly, only the processing of natural unheard formants decreases significantly with age in the visual and also in the cingulate cortex. This is not the case for the processing of the unheard speech envelope, the fundamental frequency, or the purely visual information carried by lip movements. These results show that unheard spectral fine details (along with the unheard acoustic envelope) are transformed from a mere visual to a phonological representation. Aging affects especially the ability to derive spectral dynamics at formant frequencies. As listening in noisy environments should capitalize on the ability to track spectral fine details, our results provide a novel focus on compensatory processes in such challenging situations.

Direct Cochlear Recordings in Humans Show a Theta Rhythmic Modulation of Auditory Nerve Activity by Selective Attention.

The architecture of the efferent auditory system enables prioritization of strongly overlapping spatiotemporal cochlear activation patterns elicited by relevant and irrelevant inputs. So far, attempts at finding such attentional modulations of cochlear activity delivered indirect insights in humans or required direct recordings in animals. The extent to which spiral ganglion cells forming the human auditory nerve are sensitive to selective attention remains largely unknown. We investigated this question by testing the effects of attending to either the auditory or visual modality in human cochlear implant (CI) users (3 female, 13 male). Auditory nerve activity was directly recorded with standard CIs during a silent (anticipatory) cue-target interval. When attending the upcoming auditory input, ongoing auditory nerve activity within the theta range (5-8 Hz) was enhanced. Crucially, using the broadband signal (4-25 Hz), a classifier was even able to decode the attended modality from single-trial data. Follow-up analysis showed that the effect was not driven by a narrow frequency in particular. Using direct cochlear recordings from deaf individuals, our findings suggest that cochlear spiral ganglion cells are sensitive to top-down attentional modulations. Given the putatively broad hair-cell degeneration of these individuals, the effects are likely mediated by alternative efferent pathways compared with previous studies using otoacoustic emissions. Successful classification of single-trial data could additionally have a significant impact on future closed-loop CI developments that incorporate real-time optimization of CI parameters based on the current mental state of the user.SIGNIFICANCE STATEMENT The efferent auditory system in principle allows top-down modulation of auditory nerve activity; however, evidence for this is lacking in humans. Using cochlear recordings in participants performing an audiovisual attention task, we show that ongoing auditory nerve activity in the silent cue-target period is directly modulated by selective attention. Specifically, ongoing auditory nerve activity is enhanced within the theta range when attending upcoming auditory input. Furthermore, over a broader frequency range, the attended modality can be decoded from single-trial data. Demonstrating this direct top-down influence on auditory nerve activity substantially extends previous works that focus on outer hair cell activity. Generally, our work could promote the use of standard cochlear implant electrodes to study cognitive neuroscientific questions.

Degradation levels of continuous speech affect neural speech tracking and alpha power differently.

Making sense of a poor auditory signal can pose a challenge. Previous attempts to quantify speech intelligibility in neural terms have usually focused on one of two measures, namely low-frequency speech-brain synchronization or alpha power modulations. However, reports have been mixed concerning the modulation of these measures, an issue aggravated by the fact that they have normally been studied separately. We present two MEG studies analyzing both measures. In study 1, participants listened to unimodal auditory speech with three different levels of degradation (original, 7-channel and 3-channel vocoding). Intelligibility declined with declining clarity, but speech was still intelligible to some extent even for the lowest clarity level (3-channel vocoding). Low-frequency (1-7 Hz) speech tracking suggested a U-shaped relationship with strongest effects for the medium-degraded speech (7-channel) in bilateral auditory and left frontal regions. To follow up on this finding, we implemented three additional vocoding levels (5-channel, 2-channel and 1-channel) in a second MEG study. Using this wider range of degradation, the speech-brain synchronization showed a similar pattern as in study 1, but further showed that when speech becomes unintelligible, synchronization declines again. The relationship differed for alpha power, which continued to decrease across vocoding levels reaching a floor effect for 5-channel vocoding. Predicting subjective intelligibility based on models either combining both measures or each measure alone showed superiority of the combined model. Our findings underline that speech tracking and alpha power are modified differently by the degree of degradation of continuous speech but together contribute to the subjective speech understanding.