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.

Impact of Antihypertensive Medication Changes After Renal Denervation Among Different Patient Groups: SPYRAL HTN-ON MED.

BACKGROUND: The SPYRAL HTN-ON MED (Global Clinical Study of Renal Denervation With the Symplicity Spyral Multi-electrode Renal Denervation System in Patients With Uncontrolled Hypertension in the Absence of Antihypertensive Medications)trial showed significant office and nighttime systolic blood pressure (BP) reductions in patients with hypertension following renal denervation (RDN) compared with sham-control patients, despite similar 24-hour BP reductions. We compared antihypertensive medication and BP changes among prespecified subpopulations. METHODS: The multicenter, randomized, sham-controlled, blinded SPYRAL HTN-ON MED trial (n=337) evaluated BP changes after RDN compared with a sham procedure in patients with hypertension prescribed 1 to 3 antihypertensive drugs. Most patients (n=187; 54%) were enrolled outside the United States, while 156 (46%) US patients were enrolled, including 60 (18%) Black Americans. RESULTS: Changes in detected antihypertensive drugs were similar between RDN and sham group patients in the outside US cohort, while drug increases were significantly more common in the US sham group compared with the RDN group. Patients from outside the United States showed significant reductions in office and 24-hour mean systolic BP at 6 months compared with the sham group, whereas BP changes were similar between RDN and sham in the US cohort. Within the US patient cohort, Black Americans in the sham control group had significant increases in medication burden from baseline through 6 months (P=0.003) but not in the RDN group (P=0.44). CONCLUSIONS: Patients enrolled outside the United States had minimal antihypertensive medication changes between treatment groups and had significant office and 24-hour BP reductions compared with the sham group. Increased antihypertensive drug burden in the US sham cohort, especially among Black Americans, may have diluted the treatment effect in the combined trial population. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02439775.

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.

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.

Direct assessment of microcirculation in shock: a randomized-controlled multicenter study.

PURPOSE: Shock is a life-threatening condition characterized by substantial alterations in the microcirculation. This study tests the hypothesis that considering sublingual microcirculatory perfusion variables in the therapeutic management reduces 30-day mortality in patients admitted to the intensive care unit (ICU) with shock. METHODS: This randomized, prospective clinical multicenter trial-recruited patients with an arterial lactate value above two mmol/L, requiring vasopressors despite adequate fluid resuscitation, regardless of the cause of shock. All patients received sequential sublingual measurements using a sidestream-dark field (SDF) video microscope at admission to the intensive care unit (± 4 h) and 24 (± 4) hours later that was performed blindly to the treatment team. Patients were randomized to usual routine or to integrating sublingual microcirculatory perfusion variables in the therapy plan. The primary endpoint was 30-day mortality, secondary endpoints were length of stay on the ICU and the hospital, and 6-months mortality. RESULTS: Overall, we included 141 patients with cardiogenic (n = 77), post cardiac surgery (n = 27), or septic shock (n = 22). 69 patients were randomized to the intervention and 72 to routine care. No serious adverse events (SAEs) occurred. In the interventional group, significantly more patients received an adjustment (increase or decrease) in vasoactive drugs or fluids (66.7% vs. 41.8%, p = 0.009) within the next hour. Microcirculatory values 24 h after admission and 30-day mortality did not differ [crude: 32 (47.1%) patients versus 25 (34.7%), relative risk (RR) 1.39 (0.91-1.97); Cox-regression: hazard ratio (HR) 1.54 (95% confidence interval (CI) 0.90-2.66, p = 0.118)]. CONCLUSION: Integrating sublingual microcirculatory perfusion variables in the therapy plan resulted in treatment changes that do not improve survival at all.

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.

Renal Denervation for Resistant Hypertension: A Concise Update on Treatment Options and the Latest Clinical Evidence.

Evidence from recent sham-controlled trials supports the use of endovascular renal denervation (RDN) to lower blood pressure in general as well as in treatment-resistant hypertension. According to recent studies, the effects of RDN are long lasting. Newer technologies using multipolar radiofrequency catheters and an additional ablation of the renal side branches as well as ultrasound with improved circumferential tissue penetration have made these advances possible. This has initiated a change of the perspective on RDN in clinical guidelines and has thereby set a cornerstone for a broader clinical application of RDN in the future.

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.

Assessment of arterial stiffness to predict blood pressure response to renal sympathetic denervation.

BACKGROUND: Recent trials support the efficacy of renal sympathetic denervation (RDN) to reduce blood pressure (BP). Nevertheless, about one third of patients are considered non-responders to RDN. Previous retrospective analyses suggest arterial stiffness could predict BP response to RDN. AIMS: We prospectively assessed the potential of invasive pulse wave velocity (iPWV) to predict BP response to RDN. Additionally, we aimed to establish non-invasive models based on arterial stiffness to predict BP response to RDN. METHODS:  iPWV, magnetic resonance imaging-based markers of arterial stiffness and the carotid-femoral pulse wave velocity were recorded prior to RDN in patients with treatment resistant hypertension. Changes in daytime BP after 3 months were analysed according to the prespecified iPWV cut-off (14.4 m/s). Regression analyses were used to establish models for non-invasive prediction of BP response. Results were compared to iPWV as reference and were then validated in an external patient cohort. RESULTS: Eighty patients underwent stiffness assessment before RDN. After 3 months, systolic 24h and daytime BP were reduced by 13.6±9.8 mmHg and 14.7±10.6 mmHg in patients with low iPWV, versus 6.2±13.3 mmHg and 6.3±12.8 mmHg in those with high iPWV (p<0.001 for both). Upon regression analysis, logarithmic ascending aortic distensibility and systolic baseline BP independently predicted BP change at follow-up. Both were confirmed in the validation cohort. CONCLUSIONS:  iPWV is an independent predictor for BP response after RDN. In addition, BP change prediction following RDN using non-invasive measures is feasible. This could facilitate patient selection for RDN treatment.

Changes in left atrial function in patients undergoing cardioversion for atrial fibrillation: relevance of left atrial strain in heart failure.

BACKGROUND: Left atrial (LA) reservoir strain provides prognostic information in patients with and without heart failure (HF), but might be altered by atrial fibrillation (AF). The aim of the current study was to investigate changes of LA deformation in patients undergoing cardioversion (CV) for first-time diagnosis of AF. METHODS AND RESULTS: We performed 3D-echocardiography and strain analysis before CV (Baseline), after 25 ± 10 days (FU-1) and after 190 ± 20 days (FU-2). LA volumes, reservoir, conduit and active function were measured. In total, 51 patients were included of whom 35 were in SR at FU-1 (12 HF and preserved ejection fraction (HFpEF)), while 16 had ongoing recurrence of AF (9 HFpEF). LA maximum volume was unaffected by cardioversion (Baseline vs. FU-2: 41 ± 11 vs 40 ± 10 ml/m2; p = 0.85). Restored SR led to a significant increase in LA reservoir strain (Baseline vs FU-1: 12.9 ± 6.8 vs 24.6 ± 9.4, p < 0.0001), mediated by restored LA active strain (SR group Baseline vs. FU-1: 0 ± 0 vs. 12.3 ± 5.3%, p < 0.0001), while LA conduit strain remained unchanged (Baseline vs. FU-1: 12.9 ± 6.8 vs 13.1 ± 6.2, p = 0.78). Age-controlled LA active strain remained the only significant predictor of LA reservoir strain on multivariable analysis (ß 1.2, CI 1.04-1.4, p < 0.0001). HFpEF patients exhibited a significant increase in LA active (8.2 ± 4.3 vs 12.2 ± 6.6%, p = 0.004) and reservoir strain (18.3 ± 5.7 vs. 22.8 ± 8.8, p = 0.04) between FU-1 and FU-2, associated with improved LV filling (r = 0.77, p = 0.005). CONCLUSION: Reestablished SR improves LA reservoir strain by restoring LA active strain. Despite prolonged atrial stunning following CV, preserved SR might be of hemodynamic and prognostic benefit in HFpEF.

Sympathomodulation in Heart Failure with High vs. Normal Ejection Fraction.

Background: Despite recent advances in the treatment of heart failure with preserved ejection fraction (HFpEF), the overall outcome is poor and evidence-based therapeutic options are scarce. So far, the only evidence-based therapy in HFpEF, sodium glucose linked transporter 2 inhibitors, has only insignificant effects in patients with a high EF (EF > 60%, HEF) when compared to a normal EF (EF 50%-60%, NEF). This could be explained by different biomechanical and cellular phenotypes of HFpEF across the range of EFs rather than a uniform pathophysiology. We aimed to investigate the concept of different phenotypes in the HEF and NEF using noninvasive single-beat estimations and to observe alterations in pressure-volume relations in both groups following sympathomodulation using renal denervation (RDN). Methods: Patients from a previous study on RDN in HFpEF were stratified by having HFpEF with an HEF or NEF. Single-beat estimations were used to derive arterial elastance (Ea), end-systolic elastance (Ees), and diastolic capacitance (VPED20). Results: Overall, 63 patients were classified as having an HEF, and 36 patients were classified as having an NEF. Ea did not differ between the groups and was reduced at follow-up in both groups (p < 0.01). Ees was higher and VPED20 was lower in the HEF than those in the NEF. Both were changed significantly at follow-up in the HEF but not in the NEF. Ees/Ea was lower in the NEF (0.95 ± 0.22 vs 1.15 ± 0.27, p < 0.01) and was significantly increased in the NEF (by 0.08 ± 0.20, p < 0.05) but not in the HEF. Conclusions: Beneficial effects of RDN were observed in the NEF and HEF, supporting the further investigation of sympathomodulating treatments for HFpEF in future trials.

Iatrogenic Atrial Septal Defects Following Transcatheter Mitral Valve Repair and Implications of Interventional Closure.

OBJECTIVES: The authors investigated whether iatrogenic atrial septal defect (iASD) closure post-transcatheter mitral valve edge-to-edge repair (TMVR) is superior to conservative therapy (CT) and whether outcomes (death/heart failure [HF] hospitalization) differ between patients with and without an iASD post-TMVR. BACKGROUND: Transseptal access for TMVR can create an iASD, which is associated with impaired outcomes. Controversially, the creation of an iASD in HF has been linked to improved hemodynamics. METHODS: 80 patients with an iASD and relevant left-to-right shunting (Qp:Qs ≥1.3) 30 days following TMVR were randomized to CT or interventional closure of the iASD (MITHRAS [Closure of Iatrogenic Atrial Septal Defect Following Transcatheter Mitral Valve Repair] cohort), and 235 patients without an iASD served as a comparative cohort. RESULTS: All patients of the MITHRAS cohort (mean age 77 ± 9 years, 39% women) received their allocated treatment, and follow-up was completed for all MITHRAS and comparative cohort (mean age 77 ± 8 years, 47% women) patients. Twelve months post-TMVR, there was no significant difference in the combined endpoint of death or HF hospitalization within the MITHRAS cohort (iASD closure: 35% vs CT 50%; P = 0.26). The combined endpoint was more frequent among patients within the MITHRAS cohort as opposed to the comparative cohort (43% vs 17%; P < 0.0001), primarily driven by a higher rate of HF hospitalization (34% vs 8%; P = 0.004). CONCLUSIONS: In this randomized controlled trial, interventional closure of a relevant iASD 1 month after TMVR did not result in improved clinical outcomes at 12 months post-TMVR. Patients with an iASD are at higher risk for HF hospitalization independent of iASD management and warrant close follow-up. (Closure of Iatrogenic Atrial Septal Defect Following Transcatheter Mitral Valve Repair [MITHRAS]; NCT03024268).

Comparison of Long-Term Outcomes for Responders Versus Non-Responders Following Renal Denervation in Resistant Hypertension.

Background Recent trial results support the efficacy of renal sympathetic denervation in lowering blood pressure (BP). While BP reduction in general is associated with a clinically meaningful reduction in cardiovascular events and mortality, such a relationship has not been described for patients undergoing renal sympathetic denervation. Methods and Results Clinical events were assessed in patients who underwent renal sympathetic denervation at our center using telephone- and clinical follow-up, interviews with general practitioners, as well as review of hospital databases. Event rates were compared between BP responders (≥5 mm Hg 24-hour ambulatory BP reduction) and non-responders; 296 patients were included. Compared with baseline, 24-hour systolic ambulatory BP was reduced by 8.3±12.2 mm Hg and diastolic BP by 4.8±7.0 mm Hg (P<0.001 for both) after 3 months. One hundred eighty patients were classified as BP responders and 116 as non-responders. During a median follow-up time of 48 months, significantly less major adverse cardiovascular events (cardiovascular death, stroke, myocardial infarction, critical limb ischemia, renal failure) occurred in responders than in non-responders (22 versus 23 events, hazard ratio [HR], 0.53 [95% CI, 0.28 to 0.97], P=0.041). This was consistent after adjustment for potential confounders as well as confirmed by propensity-score matching. A proportional relationship was found between BP reduction after 3 months and frequency of major adverse cardiovascular events (HR, 0.75 [95% CI, 0.58 to 0.97] per 10 mm Hg 24-hour systolic ambulatory BP reduction). Conclusions Based on these observational data, blood pressure response to renal sympathetic denervation is associated with improved long-term clinical outcome.

Renal Sympathetic Denervation in Patients With Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Arterial hypertension is the most common comorbidity in patients with heart failure with preserved ejection fraction (HFpEF) and mediates adverse hemodynamics through related aortic stiffness and increased pulsatile load. We aimed to investigate the clinical and hemodynamic implications of renal sympathetic denervation (RDN) in patients with HFpEF and uncontrolled arterial hypertension. METHODS: Patients undergoing RDN between 2011 and 2018 in a single-center were retrospectively analyzed and classified as HFpEF (n=99) or no HF (n=65). Stroke volume index and aortic distensibility were measured through cardiac magnetic resonance imaging, and left ventricular (LV) systolic and diastolic properties were assessed echocardiographically. RESULTS: At baseline, patients with HFpEF had higher stroke volume index (median 40 [interquartile range, 33-48] versus 33 [26-40] mL/m2, P=0.002), pulse pressure (69 [63-77] versus 61 [55-67] mm Hg, P<0.001), but lower LV-VPES100mm Hg (18 [10-28] versus 24 [15-40] mL, P=0.007) and aortic distensibility (1.5 [1.1-2.6] versus 2.7 [1.1-3.5] 10-3 mm Hg-1, P=0.013) as compared to no-HF patients. Systolic blood pressure decreased comparable in patients with HFpEF and no-HF patients following RDN (-9 [-16 to -2], P<0.001). After RDN stroke volume index (-3 [-9 to +3] mL/m2, P=0.011) decreased and aortic distensibility (0.2 [-0.1 to +1.1] 10-3 mm Hg-1, P=0.007) and systolic stiffness (P<0.001) increased in HFpEF patients. LV diastolic stiffness and LV filling pressures as well as NT-proBNP (N-terminal pro-B-type natriuretic peptide) decreased after RDN in patients with HFpEF (P=0.032, P=0.043, and P<0.001, respectively). CONCLUSIONS: Patients with HFpEF undergoing RDN showed increased stroke volume index, vascular, and LV stiffness as compared to no-HF patients. Following RDN those hemodynamic alterations and reduced systolic and diastolic LV stiffness were partly normalized, implying RDN might be a potential therapeutic strategy for arterial hypertension and HFpEF.

Biventricular Physiology of Iatrogenic Atrial Septal Defects Following Transcatheter Mitral Valve Edge-to-Edge Repair.

OBJECTIVES: The study sought to assess the acute hemodynamic effects of iatrogenic atrial septal defect (iASD) closure following transcatheter mitral valve edge-to-edge repair (TMVR). BACKGROUND: The potential hemodynamic and clinical consequences of an iASD following TMVR are currently subject to controversial debates. METHODS: In 21 patients with relevant left-to-right shunt flow (50% [IQR: 38% to 60%] of systemic perfusion volume) across an iASD following TMVR, interventional closure was performed with recordings of left ventricular (LV) and right ventricular (RV) pressure-volume loops during iASD occlusion. RESULTS: iASD occlusion led to a volume shift from the RV (RV end-diastolic volume index: pre 102 [IQR: 80 to 120] ml/m2, post 92 [IQR: 70 to 111] ml/m2; p < 0.001) to the LV (LV end-diastolic volume index: pre 91 [IQR: 74 to 124] ml/m2, post 97 [IQR: 77 to 127] ml/m2; p < 0.001) with reduced RV (3.49 [IQR: 2.07 to 3.58] l/min/m2 vs. 2.68 [IQR: 2.07 to 3.58] l/min/m2; p < 0.001) but increased LV cardiac index (2.25 [IQR: 1.80 to 3.28] l/min/m2 vs. 2.77 [IQR: 1.90 to 3.34] l/min/m2; p = 0.039). Although RV end-diastolic pressure decreased (pre 5.0 [IQR: 4.0 to 8.5] mm Hg, post 4.5 [IQR: 3.0 to 8.3] mm Hg; p = 0.024), LV end-diastolic pressure remained unchanged (pre 11.0 [IQR: 9.5 to 14.0] mm Hg, post 13.0 [IQR: 9.0 to 15.5] mm Hg; p = 0.142). LV transmural pressure increased (7.0 [IQR: 4.0 to 11.0] mm Hg vs. 11.0 [IQR: 7.0 to 15.0] mm Hg; p = 0.001) and LV eccentricity index decreased (p < 0.001). The change in LV transmural pressure correlated significantly with the change in LV-to-RV end-diastolic volume ratio (r = 0.674; p = 0.018). Right heart failure symptoms declined at 1-month follow-up (71% vs. 35%; p = 0.003) as did New York Heart Association functional class (≥III: 48% vs. 25%; p < 0.001). CONCLUSIONS: iASD closure following TMVR leads to a volume shift from the RV to the LV with reduced pulmonary but increased systemic cardiac index and with favorable biventricular interaction at maintained LV filling pressure, resulting in a decline in heart failure symptoms at 1-month follow-up.