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.

Metastatic Penile Squamous Cell Carcinoma: Unmasked by an Acute Myocardial Infarction and Terminal Heart Failure.

A young patient, recently treated for squamous cell penile carcinoma, presented with acute myocardial infarction and severe heart failure. Despite repeatedly ruling out metastatic disease on imaging, surgery for a mechanical assist device revealed unexpected squamous cell metastasis in the pericardium. Consequently, palliative care was initiated.

Transthyretin amyloid cardiomyopathy among patients with heart failure and preserved ejection fraction: the AMY score.

AIMS: Transthyretin 'wild-type' amyloid cardiomyopathy (ATTRwt-CM) is a differential diagnosis of heart failure with preserved ejection fraction (HFpEF). The clinical work-up for ATTRwt-CM is challenging. Considering a combination of clinical variables specific for ATTRwt-CM might aid in identifying patients at risk. METHODS AND RESULTS: Sixty patients (78 ± 6 years, 8% female) were diagnosed with ATTRwt-CM by endomyocardial biopsy. Preserved ejection fraction (LVEF >45%) was present in 41 of the patients. Those were 1:1 propensity score age- and sex-matched to a cohort of patients with HFpEF. ATTRwt-CM patients had less obesity (P = 0.01) and higher septal thickness (IVSd, P < 0.01) as well as more diastolic dysfunction (E/e', P < 0.01). On multivariable regression IVSd > 14 mm, E/e' > 14 and absence of obesity (P > 0.01 for all) were identified as predictors for ATTRwt-CM. A weighted point-based score was derived with IVSd > 14 mm = 1 point; absence of obesity = 2 points; and E/e' > 14 = 3 points. Area under the curve (AUC) for the summation score was 0.91 (0.84-0.97, P < 0.01) and a score of more than 3 points predicted ATTRwt-CM with good sensitivity (78%) and specificity (90%). The score was validated in an external cohort of 142 patients with ATTRwt-CM and 419 HFpEF patients showing sufficient accuracy (AUC 0.91, 0.88-0.94, P < 0.01). A value greater than 3 points demonstrated a high sensitivity (93%) and a negative predictive value of 97%. CONCLUSIONS: A score based on basic clinical and echocardiographic features helps to distinguish ATTRwt-CM from typical HFpEF. This could facilitate the diagnostic work-up for these patients and enable earlier disease screening on a large scale.

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.

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.

Effects of tricuspid transcatheter edge-to-edge repair on tricuspid annulus diameter - Data from the TriValve registry.

AIMS: T-TEER is an effective therapy for the treatment of tricuspid regurgitation (TR). However, the effects of leaflets clipping on tricuspid valve annulus (TA) have not been investigated in detail. The aim of this study is to investigate the effects of tricuspid transcatheter edge-to-edge repair (T-TEER) on TA diameter. METHODS AND RESULTS: The TriValve registry (Transcatheter Tricuspid Valve Therapies, NCT03416166) collected 556 patients from 22 European and North American centres undergoing transcatheter tricuspid valve interventions from 2016 to 2022. Patients undergoing T-TEER with available pre- and post-procedural data on TA diameter measured in the apical 4-chamber view on transthoracic echocardiography were selected for this study. Primary end-point was the reduction of TA diameter after T-TEER. A total of 186 patients were included in the study. In 115 patients (62%) TA diameter was reduced by at least 1 mm as compared to baseline. A significant reduction of TA dimension was observed following T-TEER (mean 2.3 mm [from pre-procedural diameter 46.7 mm to post-procedural diameter 44.4 mm], p < 0.001). In particular, the greatest reduction was observed in those with T-TEER in antero-septal commissure (mean 2.7 mm [from 47.1 mm to 44.4 mm], p < 0.001) as compared to those combining both antero-septal and postero-septal commissures (mean 1.4, from 46.0 mm to 44.6 mm, P = 0.06). A significant reduction of TA dimension was recorded in patients with 1 or 2 clips implanted but not in those patients with ≥3 clips implanted. CONCLUSIONS: In almost two third of patients T-TEER reduces TA diameter in addition to leaflet approximation. CONDENSED ABSTRACT: The effects of tricuspid transcatheter edge-to-edge repair (T-TEER) on tricuspid valve annulus (TA) have not been studied in details. This study investigates TA diameter as measured in apical 4-chamber view on transthoracic echocardiography before and after T-TEER. A total of 186 patients from the TriValve registry were included in the study. The study results show that 62% of patients have a TA reduction after T-TEER, especially in those receiving 1 or 2 clips in the antero-septal commissure. These suggest that T-TEER reduces tricuspid regurgitation not only by approximation of leaflets, but also by TA diameter reduction.

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.

Prognostic significance and clinical utility of left atrial reservoir strain in transcatheter aortic valve replacement.

AIMS: Patients with diastolic dysfunction (DD) experience worse outcomes after transcatheter aortic valve replacement (TAVR). We investigated the prognostic value and clinical utility of left atrial reservoir strain (LARS) in patients undergoing TAVR for aortic stenosis (AS). METHODS AND RESULTS: All consecutive patients undergoing TAVR between January 2018 and December 2018 were included if discharge echocardiography and follow-up were available. LARS was derived from 2D-speckle-tracking. Patients were grouped into three tertiles according to LARS. DD was analysed using the ASE/EACVI-algorithm. The primary outcome was a composite of all-cause death and readmission for worsening heart failure 12 months after TAVR. Overall, 606 patients were available [age 80 years, interquartile range (IQR) 77-84], including 53% women. Median LARS was 13.0% (IQR 8.4-18.3). Patients were classified by LARS tertiles [mildly impaired 21.4% (IQR 18.3-24.5), moderately impaired 13.0% (IQR 11.3-14.6), severely impaired 7.1% (IQR 5.4-8.4), P < 0.0001]. The primary outcome occurred more often in patients with impaired LARS (mildly impaired 7.4%, moderately impaired 13.4%, and severely impaired 25.7%, P < 0.0001). On adjusted multivariable Cox regression analysis, LARS tertiles [hazard ratio (HR) 0.62, 95% confidence interval (CI) 0.44-0.86, P = 0.005] and higher degree of tricuspid regurgitation (HR 1.82, 95% CI 1.23-2.98, P = 0.003) were the only significant predictors of the primary endpoint. Importantly, DD was unavailable in 56% of patients, but LARS assessment allowed for reliable prognostication regarding the primary endpoint in subgroups without DD assessment (HR 0.64, 95% CI 0.47-0.87, P = 0.003). CONCLUSION: Impaired LARS is independently associated with worse outcomes in patients undergoing TAVR. LARS allows for risk stratification at discharge even in patients where DD cannot be assessed by conventional echocardiographic means.

Treatment response to spironolactone in patients with heart failure with preserved ejection fraction: a machine learning-based analysis of two randomized controlled trials.

BACKGROUND: Whether there is a subset of patients with heart failure with preserved ejection fraction (HFpEF) that benefit from spironolactone therapy is unclear. We applied a machine learning approach to identify responders and non-responders to spironolactone among patients with HFpEF in two large randomized clinical trials. METHODS: Using a reiterative cluster allocating permutation approach, patients from the derivation cohort (Aldo-DHF) were identified according to their treatment response to spironolactone with respect to improvement in E/e'. Heterogenous features of response ('responders' and 'non-responders') were characterized by an extreme gradient boosting (XGBoost) algorithm. XGBoost was used to predict treatment response in the validation cohort (TOPCAT). The primary endpoint of the validation cohort was a combined endpoint of cardiovascular mortality, aborted cardiac arrest, or heart failure hospitalization. Patients with missing variables for the XGboost model were excluded from the validation analysis. FINDINGS: Out of 422 patients from the derivation cohort, reiterative cluster allocating permutation identified 159 patients (38%) as spironolactone responders, in whom E/e' significantly improved (p = 0.005). Within the validation cohort (n = 525) spironolactone treatment significantly reduced the occurrence of the primary outcome among responders (n = 185, p log rank = 0.008), but not among patients in the non-responder group (n = 340, p log rank = 0.52). INTERPRETATION: Machine learning approaches might aid in identifying HFpEF patients who are likely to show a favorable therapeutic response to spironolactone. FUNDING: See Acknowledgements section at the end of the manuscript.

Webtool to enhance the accuracy of diagnostic algorithms for HFpEF: a prospective cross-over study.

AIMS: Diagnosis of heart failure with preserved ejection fraction (HFpEF) can be challenging. This study aimed to evaluate the potential of a webtool to enhance the scoring accuracy when applying the complex HFA-PEFF and H2 FPEF algorithms, which are commonly used for diagnosing HFpEF. METHODS AND RESULTS: We developed an online tool, the HFpEF calculator, that enables the automatic calculation of current HFpEF algorithms. We assessed the accuracy of manual vs. automatic scoring, defined as the percentage of correct scores, in a cohort of cardiologists with varying clinical experience. Cardiologists scored eight online clinical cases using a triple cross-over design (i.e. two manual-two automatic-two manual-two automatic). Data were analysed in study completers (n = 55, 29% heart failure specialists, 42% general cardiologists, and 29% cardiology residents). Manually calculated scores were correct in 50% (HFA-PEFF: 50% [50-75]; H2 FPEF: 50% [38-50]). Correct scoring improved to 100% using the HFpEF calculator (HFA-PEFF: 100% [88-100], P < 0.001; H2 FPEF: 100% [75-100], P < 0.001). Time spent on clinical cases was similar between scoring methods (±4 min). When corrections for faulty algorithm scores were displayed, cardiologists changed their diagnostic decision in up to 67% of cases. At least 67% of cardiologists preferred using the online tool for future cases in clinical practice. CONCLUSIONS: Manual calculation of HFpEF diagnostic algorithms is often inaccurate. Using an automated webtool to calculate HFpEF algorithms significantly improved correct scoring. This new approach may impact the eventual diagnostic decision in up to two-thirds of cases, supporting its routine use in clinical practice.

Stressed Blood Volume in Severe Tricuspid Regurgitation: Implications for Transcatheter Treatment.

BACKGROUND: Although tricuspid transcatheter edge-to-edge repair (TEER) has been suggested to improve outcomes in patients with tricuspid regurgitation (TR), patients remain at substantial residual risk after the intervention. Total blood volume is divided between the unstressed volume, filling the vascular space, and stressed blood volume (SBV), generating intravascular pressure. SBV is an important mediator of hemodynamic derangements in heart failure and might pose an attractive adjunctive treatment target. OBJECTIVES: The aim of this study was to investigate the role of SBV in patients with severe TR and its implications for tricuspid TEER. METHODS: In total, 279 patients underwent right heart catheterization prior to TEER. SBV was estimated from hemodynamic variables fit to a comprehensive cardiovascular model. RESULTS: Estimated stressed blood volume (eSBV) was associated with obesity, renal and hepatic dysfunction and cardiac remodeling (P < 0.05 for all). Hemodynamically, eSBV correlated with pulmonary artery and cardiac filling pressures as well as right ventricular-pulmonary artery coupling (P < 0.05 for all). After TEER, patients with eSBV greater than the median demonstrated less reduction in right atrial pressures, peripheral edema, and ascites compared with lower eSBV patients (P < 0.05 for all). Higher eSBV was an independent predictor of the occurrence of death and heart failure hospitalization during a median follow-up duration of 618 days (P < 0.05 for all). CONCLUSIONS: In patients with severe TR, eSBV is associated with obesity, renal and liver dysfunction, more severe heart failure, attenuated reduction of venous congestion after TEER, and adverse clinical outcomes. Estimation of SBV should be incorporated in future trials in the field to identify patients in need of adjunctive therapies.

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.

Prognostic Value of Tricuspid Valve Gradient After Transcatheter Edge-to-Edge Repair: Insights From the TriValve Registry.

BACKGROUND: Data regarding the impact of the tricuspid valve gradient (TVG) after tricuspid transcatheter edge-to-edge repair (TEER) are scarce. OBJECTIVES: This study sought to evaluate the association between the mean TVG and clinical outcomes among patients who underwent tricuspid TEER for significant tricuspid regurgitation. METHODS: Patients with significant tricuspid regurgitation who underwent tricuspid TEER within the TriValve (International Multisite Transcatheter Tricuspid Valve Therapies) registry were divided into quartiles based on the mean TVG at discharge. The primary endpoint was the composite of all-cause mortality and heart failure hospitalization. Outcomes were assessed up to the 1-year follow-up. RESULTS: A total of 308 patients were included from 24 centers. Patients were divided into quartiles of the mean TVG as follows: quartile 1 (n = 77), 0.9 ± 0.3 mm Hg; quartile 2 (n = 115), 1.8 ± 0.3 mm Hg; quartile 3 (n = 65), 2.8 ± 0.3 mm Hg; and quartile 4 (n = 51), 4.7 ± 2.0 mm Hg. The baseline TVG and the number of implanted clips were associated with a higher post-TEER TVG. There was no significant difference across TVG quartiles in the 1-year composite endpoint (quartiles 1-4: 35%, 30%, 40%, and 34%, respectively; P = 0.60) or the proportion of patients in New York Heart Association class III to IV at the last follow-up (P = 0.63). The results were similar after adjustment for clinical and echocardiographic characteristics (composite endpoint quartile 4 vs quartile 1-quartile 3 adjusted HR: 1.05; 95% CI: 0.52-2.12; P = 0.88) or exploring post-TEER TVG as a continuous variable. CONCLUSIONS: In this retrospective analysis of the TriValve registry, an increased discharge TVG was not significantly associated with adverse outcomes after tricuspid TEER. These findings apply for the explored TVG range and up to the 1-year follow-up. Further investigations on higher gradients and longer follow-up are needed to better guide the intraprocedural decision-making process.

Sex-related characteristics and short-term outcomes of patients undergoing transcatheter tricuspid valve intervention for tricuspid regurgitation.

AIMS: The impact of sexuality in patients with significant tricuspid regurgitation (TR) undergoing transcatheter tricuspid valve intervention (TTVI) is unknown. The aim of this study was to investigate sex-specific outcomes in patients with significant TR treated with TTVI vs. medical therapy alone. METHODS AND RESULTS: The Transcatheter Tricuspid Valve Therapies (TriValve) registry collected data on patients with significant TR from 24 centres who underwent TTVI from 2016 to 2021. A control cohort was formed by medically managed patients with ≥severe isolated TR diagnosed in 2015-18. The primary endpoint was freedom from all-cause mortality. Secondary endpoints were heart failure (HF) hospitalization, New York Heart Association (NYHA) functional status, and TR severity. One-year outcomes were assessed for the TriValve cohort and compared with the control cohort with the inverse probability of treatment weighting (IPTW). A total of 556 and 2072 patients were included from the TriValve and control groups, respectively. After TTVI, there was no difference between women and men in 1-year freedom from all-cause mortality 80.9% vs. 77.9%, P = 0.56, nor in HF hospitalization (P = 0.36), NYHA Functional Classes III and IV (P = 0.17), and TR severity >2+ at last follow-up (P = 0.42). Multivariable Cox-regression weighted by IPTW showed improved 1-year survival after TTVI compared with medical therapy alone in both women (adjusted hazard ratio 0.45, 95% confidence interval 0.23-0.83, P = 0.01) and men (adjusted hazard ratio 0.42, 95% confidence interval 0.18-0.89, P = 0.03). CONCLUSION: After TTVI in high-risk patients, there were no sex-related differences in terms of survival, HF hospitalization, functional status, and TR reduction up to 1 year. The IPTW analysis shows a survival benefit of TTVI over medical therapy alone in both women and men.

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.