Left Ventricular Filling Pressure in Chronic Thromboembolic Pulmonary Hypertension

BackgroundChronic thromboembolic pulmonary hypertension (CTEPH) is characterized by obstruction of major pulmonary arteries with organized thrombi. Clinical risk factors for pulmonary hypertension due to left heart disease including metabolic syndrome, left-sided valvular heart disease, and ischemic heart disease are common in CTEPH patients.ObjectivesThe authors sought to investigate prevalence and prognostic implications of elevated left ventricular filling pressures (LVFP) in CTEPH.MethodsA total of 593 consecutive CTEPH patients undergoing a first diagnostic right and left heart catheterization were included in this study. Mean pulmonary arterial wedge pressure (mPAWP) and left ventricular end-diastolic pressure (LVEDP) were utilized for assessment of LVFP. Two cutoffs were applied to identify patients with elevated LVFP: 1) for the primary analysis mPAWP and/or LVEDP >15 mm Hg, as recommended by the current pulmonary hypertension guidelines; and 2) for the secondary analysis mPAWP and/or LVEDP >11 mm Hg, representing the upper limit of normal. Clinical and echocardiographic features, and long-term mortality were assessed.ResultsLVFP was >15 mm Hg in 63 (10.6%) and >11 mm Hg in 222 patients (37.4%). Univariable logistic regression analysis identified age, systemic hypertension, diabetes, atrial fibrillation, calcific aortic valve stenosis, mitral regurgitation, and left atrial volume as significant predictors of elevated LVFP. Atrial fibrillation, calcific aortic valve stenosis, mitral regurgitation, and left atrial volume remained independent determinants of LVFP in adjusted analysis. At follow-up, higher LVFPs were measured in patients who had meanwhile undergone pulmonary endarterectomy (P = 0.002). LVFP >15 mm Hg (P = 0.021) and >11 mm Hg (P = 0.006) were both associated with worse long-term survival.ConclusionsElevated LVFP is common, appears to be due to comorbid left heart disease, and predicts prognosis in CTEPH.     

Right-to-Left Shunt Through Iatrogenic Atrial Septal Defect After MitraClip Procedure

ObjectivesThe aim of this study was to investigate the incidence, characteristics, hemodynamic conditions, and clinical significance of right-to-left (R-L) shunt through an iatrogenic atrial septal defect (iASD) after the MitraClip procedure.BackgroundR-L shunt through an iASD after the MitraClip procedure has not been well investigated.MethodsFrom 2014 to 2017, 385 consecutive patients with mitral regurgitation underwent the MitraClip procedure. iASD was assessed using intraprocedural transesophageal echocardiography. Right and left heart catheterization was used to assess the hemodynamic status of patients. All patients provided written informed consent for the procedure. All data for this study were collected from an established interventional cardiology laboratory database approved by the Cedars-Sinai Medical Center Institutional Review Board.ResultsR-L shunt was observed in 20 patients (5%). In 7 of these patients (35%), R-L shunt was accompanied by acute deoxygenation. Prevalence of severe tricuspid regurgitation (55% vs. 20%; p = 0.001), serum B-type natriuretic peptide (664 pg/ml [434 to 1,169 pg/ml] vs. 400 pg/ml [195 to 699 pg/ml]; p = 0.006), mean pulmonary artery pressure (38 mm Hg [34 to 45 mm Hg] vs. 29 mm Hg [22 to 37 mm Hg]; p < 0.001), and right atrial pressure (19 mm Hg [13 to 20 mm Hg] vs. 10 mm Hg [7 to 14 mm Hg]; p < 0.001) were significantly higher in patients with R-L shunt than in those with left-to-right shunt. Patients with R-L shunt also showed a more prominent reduction in the left atrial V-wave and mean pressure from baseline to post-procedure compared with those with left-to-right shunt (−22.8 ± 2.6 mm Hg vs. −11.8 ± 0.9 mm Hg [p = 0.002] and −7.9 ± 0.8 mm Hg vs. −4.0 ± 0.4 mm Hg [p = 0.003], respectively).ConclusionsR-L shunt through an iASD was observed in 5% of patients who underwent the MitraClip procedure and in one-third of patients with R-L shunt presented acute deoxygenation. Elevated right atrial pressure concomitant with pulmonary hypertension and significant reduction in left atrial pressure after MitraClip deployment were associated with R-L shunt.     

Watchman Occlusion in Long-Standing Persistent Atrial Fibrillation: Larger Left Atrial Appendages With Greater Residual Leak

ObjectivesThis study sought to compare patients with and without long-standing persistent atrial fibrillation (LSPAF) undergoing Watchman left atrial appendage (LAA) occlusion.BackgroundAn increased burden of atrial fibrillation is associated with progressive left atrial remodeling and enlargement.MethodsTransesophageal echocardiography (TEE) measures of LAA ostial diameter and depth, device compression, and residual leak were evaluated in 101 consecutive Watchman cases. The patients were categorized into LSPAF (n = 48) or non-LSPAF (n = 53) groups and compared.ResultsThe average LAA ostial diameter for LSPAF versus non-LSPAF by TEE omniplane at 0° was 21.1 ± 4.1 mm versus 18.2 ± 3.6 mm (p = 0.0002); at 45° was 18.7 ± 3.4 mm versus 16.3 ± 3.1 mm (p = 0.0004); at 90° was 19.6 ± 3.8 mm versus 16.2 ± 3.4 mm (p = 0.00001); and at 135° was 21.0 ± 4.1 mm versus 18.0 ± 4.1 mm (p = 0.0005). The average LAA depth for LSPAF versus non-LSPAF by TEE at 0° was 28.1 ± 6.4 mm versus 25.2 ± 4.9 mm (p = 0.02); at 45° was 27.9 ± 5.8 mm versus 25.1 ± 4.3 mm (p = 0.007); at 90° was 27.2 ± 5.2 mm versus 22.8 ± 3.7 mm (p = 0.0001); and at 135° was 25.6 ± 5.4 mm versus 21.5 ± 3.8 mm (p = 0.0001). In successfully treated patients, 77% of the LSPAF group received larger device (27, 30, or 33 mm) implants versus only 46% in the non-LSPAF group (p = 0.003). While both groups had similar rates of moderate (3 to 5 mm) leaks at implant (2% vs. 0%; p = 0.14), 27% of the LSPAF vs. 4% of the non-LSPAF group had moderate leaks (p = 0.04) on 6-week follow-up TEE.ConclusionsPatients with LSPAF have significantly larger LAA sizes, require larger devices, and have more residual leak on follow-up TEE. LSPAF may represent a higher risk group that warrants more stringent long-term follow-up.     

Effect of Mitral Valve Gradient After MitraClip on Outcomes in Secondary Mitral Regurgitation: Results From the COAPT Trial

ObjectivesThe authors sought to evaluate the association between mean mitral valve gradient (MVG) and clinical outcomes among patients who underwent MitraClip treatment for secondary mitral regurgitation (SMR) in the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation) trial.BackgroundIn the COAPT trial, patients with heart failure (HF) and severe SMR who remained symptomatic despite guideline-directed medical therapy had marked 2-year reductions in mortality and HF hospitalizations after treatment with MitraClip.MethodsMitraClip-treated patients were divided into quartiles (Q) based on discharge echocardiographic MVG (n = 250). Endpoints including all-cause mortality, HF hospitalization, and health status measures at 2 years were compared between quartiles.ResultsMean MVG after MitraClip was 2.1 ± 0.4 mm Hg, 3.0 ± 0.2 mm Hg, 4.2 ± 0.5 mm Hg, and 7.2 ± 2.0 mm Hg in Q1 (n = 63), Q2 (n = 61), Q3 (n = 62), and Q4 (n = 64), respectively. There was no difference across quartiles in the 2-year composite endpoint of all-cause mortality or HF hospitalization (43.2%, 49.2%, 40.6%, and 40.9%, respectively; p = 0.80), nor in improvements in New York Heart Association functional class, Kansas City Cardiomyopathy Questionnaire score, or 6-min walk time. Results were similar after adjustment for baseline clinical and echocardiographic characteristics, post-procedure MR grade, and number of clips (all-cause mortality or HF hospitalization Q4 [44.6%] vs. Q1 to Q3 [40.3%]; adjusted hazard ratio: 1.23, 95% confidence interval: 0.60 to 2.51; p = 0.57).ConclusionsAmong HF patients with severe SMR, higher MVGs on discharge did not adversely affect clinical outcomes following MitraClip. These findings suggest that in select patients with HF and SMR otherwise meeting the COAPT inclusion criteria, the benefits of MR reduction may outweigh the effects of mild-to-moderate mitral stenosis after MitraClip.     

Physiological Stratification of Patients With Angina Due to Coronary Microvascular Dysfunction

BackgroundCoronary microvascular dysfunction (CMD) is defined by diminished flow reserve. Functional and structural CMD endotypes have recently been described, with normal and elevated minimal microvascular resistance, respectively.ObjectivesThis study determined the mechanism of altered resting and maximal flow in CMD endotypes.MethodsA total of 86 patients with angina but no obstructive coronary disease underwent coronary pressure and flow measurement during rest, exercise, and adenosine-mediated hyperemia and were classified as the reference group or as patients with CMD by a coronary flow reserve threshold of 2.5; functional or structural endotypes were distinguished by a hyperemic microvascular resistance threshold of 2.5 mm Hg/cm/s. Endothelial function was assessed by forearm blood flow (FBF) response to acetylcholine, and nitric oxide synthase (NOS) activity was defined as the inverse of FBF reserve to N^G-monomethyl-L-arginine.ResultsOf the 86 patients, 46 had CMD (28 functional, 18 structural), and 40 patients formed the reference group. Resting coronary blood flow (CBF) (24.6 ± 2.0 cm/s vs. 16.6 ± 3.9 cm/s vs. 15.1 ± 4.7 cm/s; p < 0.001) and NOS activity (2.27 ± 0.96 vs. 1.77 ± 0.59 vs. 1.30 ± 0.16; p < 0.001) were higher in the functional group compared with the structural CMD and reference groups, respectively. The structural group had lower acetylcholine FBF augmentation than the functional or reference group (2.1 ± 1.8 vs. 4.1 ± 1.7 vs. 4.5 ± 2.0; p < 0.001). On exercise, oxygen demand was highest (rate−pressure product: 22,157 ± 5,497 beats/min/mm Hg vs. 19,519 ± 4,653 beats/min/mm Hg vs. 17,530 ± 4,678 beats/min/mm Hg; p = 0.004), but peak CBF was lowest in patients with structural CMD compared with the functional and reference groups.ConclusionsFunctional CMD is characterized by elevated resting flow that is linked to enhanced NOS activity. Patients with structural CMD have endothelial dysfunction, which leads to diminished peak CBF augmentation and increased demand during exercise. The value of pathophysiologically stratified therapy warrants investigation.     

Phase 2 Study of Aficamten in Patients With Obstructive Hypertrophic Cardiomyopathy

BackgroundLeft ventricular outflow tract (LVOT) obstruction is a major determinant of heart failure symptoms in obstructive hypertrophic cardiomyopathy (oHCM). Aficamten, a next-in-class cardiac myosin inhibitor, may lower gradients and improve symptoms in these patients.ObjectivesThis study aims to evaluate the safety and efficacy of aficamten in patients with oHCM.MethodsPatients with oHCM and LVOT gradients ≥30 mm Hg at rest or ≥50 mm Hg with Valsalva were randomized 2:1 to receive aficamten (n = 28) or placebo (n = 13) in 2 dose-finding cohorts. Doses were titrated based on gradients and ejection fraction (EF). Safety and changes in gradient, EF, New York Heart Association functional class, and cardiac biomarkers were assessed over a 10-week treatment period and after a 2-week washout.ResultsFrom baseline to 10 weeks, aficamten reduced gradients at rest (mean difference: ?40 ± 27 mm Hg, and ?43 ± 37 mm Hg in Cohorts 1 and 2, P = 0.0003 and P = 0.0004 vs placebo, respectively) and with Valsalva (?36 ± 27 mm Hg and ?53 ± 44 mm Hg, P = 0.001 and <0.0001 vs placebo, respectively). There were modest reductions in EF (?6% ± 7.5% and ?12% ± 5.9%, P = 0.007 and P < 0.0001 vs placebo, respectively). Symptomatic improvement in ≥1 New York Heart Association functional class was observed in 31% on placebo, and 43% and 64% on aficamten in Cohorts 1 and 2, respectively (nonsignificant). With aficamten, N-terminal pro–B-type natriuretic peptide was reduced (62% relative to placebo, P = 0.0002). There were no treatment interruptions and adverse events were similar between treatment arms.ConclusionsAficamten resulted in substantial reductions in LVOT gradients with most patients experiencing improvement in biomarkers and symptoms. These results highlight the potential of sarcomere-targeted therapy for treatment of oHCM.     

Transcatheter Self-Expandable Valve Implantation for Aortic Stenosis in Small Aortic Annuli: The TAVI-SMALL Registry

ObjectivesThe aim of this study was to evaluate and compare the outcomes of transcatheter self-expandable prostheses in patients with small annuli.BackgroundTranscatheter aortic heart valves appear to have better performance than surgical valves in terms of prosthesis-patient mismatch, especially in patients with aortic stenosis with small aortic annuli.MethodsTAVI-SMALL (International Multicenter Registry to Evaluate the Performance of Self-Expandable Valves in Small Aortic Annuli) is a retrospective registry of patients with severe aortic stenosis and small annuli (annular perimeter <72 mm or area <400 mm² on computed tomography) treated with transcatheter self-expandable valves (n = 859; Evolut R, n = 397; Evolut PRO, n = 84; ACURATE, n = 201; Portico, n = 177). Primary endpoints were post-procedural mean aortic gradient, indexed effective orifice area, and rate of severe prosthesis-patient mismatch.ResultsPre-discharge gradients were consistently low in every group, with a slight benefit with the Evolut R (8.1 mm Hg; 95% confidence interval [CI]: 7.7 to 8.5 mm Hg) and Evolut PRO (6.9 mm Hg; 95% CI: 6.3 to 7.6 mm Hg) compared with the ACURATE (9.6 mm Hg; 95% CI: 8.9 to 10.2 mm Hg) and Portico (8.9 mm Hg; 95% CI: 8.2 to 9.6 mm Hg) groups (p < 0.001). Mean indexed effective orifice area was 1.04 cm²/m² (95% CI: 1.01 to 1.08 cm²/m²) with a trend toward lower values with the Portico. No significant differences were reported in terms of severe prosthesis-patient mismatch (overall rate 9.4%; p = 0.134), permanent pacemaker implantation (15.6%), and periprocedural and 1-year adverse events. Pre-discharge more than mild paravalvular leaks were significantly more common with the Portico (19.2%) and less common with the Evolut PRO (3.6%) compared with the Evolut R (11.8%) and ACURATE (9%) groups.ConclusionsTranscatheter self-expandable valves showed optimal clinical and echocardiographic results in patients with small aortic annuli, although supra-annular functioning transcatheter heart valves seemed to slightly outperform intra-annular functioning ones. The role of transcatheter aortic valve replacement with self-expandable valves for the treatment of aortic stenosis in patients with small annuli needs to be confirmed in larger trials.     

Renal Denervation in High-Risk Patients With Hypertension

BackgroundRenal denervation (RDN) is under investigation for treatment of uncontrolled hypertension and might represent an attractive treatment for patients with high cardiovascular (CV) risk. It is important to determine whether baseline CV risk affects the efficacy of RDN.ObjectivesThe purpose of this study was to assess blood pressure (BP) reduction and event rates after RDN in patients with various comorbidities, testing the hypothesis that RDN is effective and durable in these high-risk populations.MethodsBP reduction and adverse events over 3 years were evaluated for several high-risk subgroups in the GSR (Global proSpective registrY for syMPathetic renaL denervatIon in seleCted IndicatIons Through 3 Years Registry), an international registry of RDN in patients with uncontrolled hypertension (n = 2,652). Comparisons were made for patients age ≥65 years versus age <65 years, with versus without isolated systolic hypertension, with versus without atrial fibrillation, and with versus without diabetes mellitus. Baseline cardiovascular risk was estimated using the American Heart Association (AHA)/American College of Cardiology (ACC) atherosclerosis cardiovascular disease (ASCVD) risk score.ResultsReduction in 24-h systolic BP at 3 years was −8.9 ± 20.1 mm Hg for the overall cohort, and for high-risk subgroups, BP reduction was −10.4 ± 21.0 mm Hg for resistant hypertension, −8.7 ± 17.4 mm Hg in patients age ≥65 years, −10.2 ± 17.9 mm Hg in patients with diabetes, −8.6 ± 18.7 mm Hg in isolated systolic hypertension, −10.1 ± 20.3 mm Hg in chronic kidney disease, and −10.0 ± 19.1 mm Hg in atrial fibrillation (p < 0.0001 compared with baseline for all). BP reduction in patients with measurements at 6, 12, 24, and 36 months showed similar reductions in office and 24-h BP for patients with varying baseline ASCVD risk scores, which was sustained to 3 years. Adverse event rates at 3 years were higher for patients with higher baseline CV risk.ConclusionsBP reduction after RDN was similar for patients with varying high-risk comorbidities and across the range of ASCVD risk scores. The impact of baseline risk on clinical event reduction by RDN-induced BP changes could be evaluated in further studies. (Global proSpective registrY for syMPathetic renaL denervatIon in seleCted IndicatIons Through 3 Years Registry; NCT01534299)     

The REDUCE HTN: REINFORCE: Randomized,Sham-Controlled Trial of Bipolar Radiofrequency Renal Denervation for the Treatment of Hypertension

ObjectivesThe aim of this study was to investigate bipolar radiofrequency renal denervation in patients with hypertension not receiving medications at baseline.BackgroundA blood pressure–reducing effect of renal denervation has been difficult to isolate in clinical investigations.MethodsREDUCE HTN: REINFORCE (Renal Denervation Using the Vessix Renal Denervation System for the Treatment of Hypertension) was a randomized, sham-controlled multicenter trial. Patients with office systolic blood pressure (SBP) of 150 to 180 mm Hg and average 24-h ambulatory SBP of 135 to 170 mm Hg after medication washout underwent bipolar radiofrequency renal denervation or a sham procedure. The planned outcome was 8-week change in 24-h ambulatory SBP. Enrollment was terminated for apparent futility before a sufficient sample for powered efficacy comparisons was enrolled. Safety assessments included all-cause death, renal failure, severe hypotension or syncope, hypertensive crisis, and renal artery stenosis.ResultsBaseline 24-h blood pressure was 148.3 ± 10.9/85.7 ± 9.1 mm Hg for the denervation group (n = 34, mean age 58.5 ± 10.1 years, 47% women) and 149.1 ± 7.2/86.4 ± 9.8 mm Hg for the control group (n = 17, mean age 58.2 ± 9.8 years, 24% women). At 8 weeks, mean 24-h SBP reductions for the renal denervation and control groups were −5.3 mm Hg (95% confidence interval [CI]: −8.8 to −1.8 mm Hg) and −8.5 mm Hg (95% CI: −13.3 to −3.8 mm Hg), respectively (difference 3.3 mm Hg; 95% CI: −2.8 to 9.3 mm Hg; p = 0.30). Antihypertensive medications could then be added. By 6 months, decreases in SBP were greater for the denervation group, yielding between-group differences of −7.2 mm Hg (95% CI: −15.2 to 0.8 mm Hg; p = 0.08), −9.7 mm Hg (95% CI: −17.7 to −1.7 mm Hg; p = 0.02), and −11.4 mm Hg (95% CI: −19.2 to −3.7 mm Hg; p < 0.01) for 24-h, daytime ambulatory, and office measurements, respectively. Through 12 months, 1 patient (renal denervation group) had a hypertensive urgency requiring immediate management, and 1 experienced progression of renal artery stenosis.ConclusionsFuture studies of radiofrequency renal denervation must anticipate delayed treatment effects. (Renal Denervation Using the Vessix Renal Denervation System for the Treatment of Hypertension [REDUCE HTN: REINFORCE]; NCT02392351)     

Subclinical Pulmonary Congestion and Abnormal Hemodynamics in Heart Failure With Preserved Ejection Fraction

ObjectivesThe authors hypothesized that quantitative computed tomography (QCT) imaging would reveal subclinical increases in lung congestion in patients with heart failure and preserved ejection fraction (HFpEF) and that this would be related to pulmonary vascular hemodynamic abnormalities.BackgroundGross evidence of lung congestion on physical examination, laboratory tests, and radiography is typically absent among compensated ambulatory patients with HFpEF. However, pulmonary gas transfer abnormalities are commonly observed and associated with poor outcomes.MethodsPatients referred for invasive hemodynamic exercise testing who had undergone chest computed tomography imaging within 1 month were identified (N = 137). A novel artificial intelligence QCT algorithm was used to measure pulmonary fluid content.ResultsCompared with control subjects with noncardiac dyspnea, patients with HFpEF displayed increased mean lung density (–758 HU [–793, –709 HU] vs –787 HU [–828, –747 HU]; P = 0.002) and a higher ratio of extravascular lung water to total lung volume (EVLWV/TLV) (1.25 [0.80, 1.76] vs 0.66 [0.01, 1.03]; P < 0.0001) by QCT imaging, indicating greater lung congestion. EVLWV/TLV was directly correlated with pulmonary vascular pressures at rest, with stronger correlations observed during exercise. Patients with increasing tertiles of EVLWV/TLV demonstrated higher mean pulmonary artery pressures at rest (34 ± 11 mm Hg vs 39 ± 14 mm Hg vs 45 ± 17 mm Hg; P = 0.0003) and during exercise (55 ± 17 mm Hg vs 59 ± 17 mm Hg vs 69 ± 22 mm Hg; P = 0.0003).ConclusionsQCT imaging identifies subclinical lung congestion in HFpEF that is not clinically apparent but is related to abnormalities in pulmonary vascular hemodynamics. These data provide new insight into the long-term effects of altered hemodynamics on pulmonary structure and function in HFpEF.     

Sex Differences in LV Remodeling and Hemodynamics in Aortic Stenosis: Sex-Specific Criteria for Severe Stenosis?

BackgroundThe current criteria for aortic stenosis (AS) severity have not incorporated sex-related differences.ObjectivesThe authors investigated sex-related serial changes in left ventricular (LV) structure/function and hemodynamics in AS.MethodsSerial echocardiograms of patients with severe AS (time 0; aortic valve area [AVA] ≤1 cm²) and ≥1 previous echocardiogram were compared between sexes.ResultsOf 927 patients (time 0: AVA 0.87 ± 0.11 cm², peak velocity 4.03 ± 0.65 m/s, mean Doppler systolic pressure gradient [MG] 40.6 ± 13.1 mm Hg), 393 (42%) were women. Women had smaller body surface area (BSA) (1.77 ± 0.22 m² vs 2.03 ± 0.20 m²; P < 0.001), lower stroke volume (SV) (81.1 ± 17.2 mL vs 88.3 ± 18.6 mL; P < 0.001), and more frequent low-gradient severe AS (n = 196 [50%] vs n = 181 [34%]; P < 0.001). Women consistently had smaller AVA, indexed AVA (AVAi), peak velocity, and MG than men. The difference in aortic valve gradient lessened when AVAi ≤0.6 cm²/m² was applied as severe AS (n = 694, women 43%, AVA 0.95 ± 0.17 cm², AVAi 0.50 ± 0.07 cm²/m²). Peak velocity (3.83 ± 0.66 m/s) and MG (36.5 ± 13.2 mm Hg) were lower based on AVAi severity criteria compared to those based on AVA. Men had a lower left ventricular ejection fraction (LVEF) (55.8% ± 14.8% vs 61.1% ± 11.7%; P < 0.001) and greater reduction in SV (?13.3 ± 19.6 mL vs ?7.4 ± 16.4 mL; P < 0.001) as AS progressed from moderate to severe. Concentric LV hypertrophy was more common and E/e? higher in women (21.2 ± 10.9 vs 18.8 ± 9.1; P < 0.001). SV, LVEF, AVA, peak velocity, and MG became precipitously worse when AVA reached 1.2 cm² in both sexes.ConclusionsSmaller BSA in women yields lower SV, resulting in lower aortic valve gradient than men. Indexed parameters by BSA are thus important in sex-related differences of aortic valve hemodynamics, but AVAi ≤0.6 cm²/m² includes individuals with moderate AS. Elevated filling pressure is more common in women. Men experience a larger reduction in SV and LVEF as AS progresses. The definition of AS severity may require different criteria between sexes.     

5-Year Outcomes With Self-Expanding vs Balloon-Expandable Transcatheter Aortic Valve Replacement in Patients With Small Annuli

BackgroundSelf-expanding transcatheter heart valves (THVs) are associated with better echocardiographic hemodynamic performance than balloon-expandable THVs and are considered preferable in patients with small annuli.ObjectivesThis study sought to compare 5-year outcomes between self-expanding vs balloon-expandable THVs in severe aortic stenosis (AS) patients with small annuli.MethodsConsecutive severe AS patients with an aortic valve annulus area <430 mm² who underwent transcatheter aortic valve replacement (TAVR) with either the CoreValve Evolut (Medtronic) or SAPIEN (Edwards Lifesciences) THV between 2012 and 2021 were enrolled from the Bern TAVI registry. A 1:1 propensity-matched analysis was performed to account for baseline differences between groups.ResultsA total of 723 patients were included, and propensity score matching resulted in 171 pairs. Technical success was achieved in over 85% of both groups with no significant difference. Self-expanding THVs were associated with a lower transvalvular gradient (8.0 ± 4.8 mm Hg vs 12.5 ± 4.5 mm Hg; P < 0.001), a larger effective orifice area (1.81 ± 0.46 cm² vs 1.49 ± 0.42 cm²; P < 0.001), and a lower incidence of prosthesis-patient mismatch (19.7% vs 51.8%; P < 0.001) than balloon-expandable THVs. At 5 years, there were no significant differences in mortality (50.4% vs 39.6%; P = 0.269) between groups. Disabling stroke occurred more frequently in patients with a self-expanding THV than those with a balloon-expandable THV (6.6% vs 0.6%; P = 0.030). Similar results were obtained using inverse probability of treatment weighting in the Bern TAVI registry and the nationwide Swiss TAVI registry.ConclusionsThe echocardiographic hemodynamic advantage of self-expanding THVs was not associated with better clinical outcomes compared with balloon-expandable THVs up to 5 years in patients with small annuli. (Swiss TAVI Registry; NCT01368250)     

Prognostic Value of Increased Mitral Valve Gradient After Transcatheter Edge-to-Edge Repair for Primary Mitral Regurgitation

ObjectivesThis study sought to evaluate the prognostic value of an increased mean mitral valve pressure gradient (MVG) in patients with primary mitral regurgitation (MR) after transcatheter edge-to-edge repair (TEER).BackgroundConflicting data exist regarding impact of increased mean MVG on outcomes after TEER.MethodsThis study included 419 patients with primary MR (mean age 80.6 ± 10.4 years; 40.6% female) who underwent TEER. Patients were divided into quartiles (Qs) based on discharge echocardiographic mean MVG. Primary outcome was the composite endpoint of all-cause mortality and heart failure hospitalization. Secondary outcomes included all-cause mortality and the secondary composite endpoint of all-cause mortality, heart failure hospitalization, and mitral valve reintervention.ResultsThe median number of MitraClips used was 2 per patient. MR reduction ≤moderate was achieved in 407 (97.1%) patients. Mean MVG was 1.9 ± 0.3 mm Hg, 3.0 ± 0.1 mm Hg, 4.0 ± 0.1 mm Hg, and 6.0 ± 1.2 mm Hg in Q1, Q2, Q3, and Q4, respectively. There was no significant differences across quartiles in the primary outcome (15.4%, 19.6%, 22.0%, and 21.9% in Q1-Q4, respectively; P = 0.63), all-cause mortality (15.9% vs 18.6% vs 19.4% vs 17.1%, respectively; P = 0.91), and the secondary composite endpoint at 2 years (33.3% vs 29.5% vs 22.0% vs 31.6%, respectively; P = 0.37). After multivariate adjustment for baseline clinical and procedural variables, the mean MVG in Q4 compared with Q1 to Q3 was not independently associated with the primary outcome (HR: 1.22; 95% CI: 0.82-1.83; P = 0.33), all-cause mortality, and the secondary composite endpoint.ConclusionsIncreased mean MVG was not independently associated with adverse events after TEER in patients with primary MR.     

Aldosterone-Related Myocardial Extracellular Matrix Expansion in Hypertension in Humans: A Proof-of-Concept Study by Cardiac Magnetic Resonance

ObjectivesThis study sought to assess the respective effects of aldosterone and blood pressure (BP) levels on myocardial fibrosis in humans.BackgroundExperimentally, aldosterone promotes left ventricular (LV) hypertrophy, and interstitial myocardial fibrosis in the presence of high salt intake.MethodsThe study included 20 patients with primary aldosteronism (PA) (high aldosterone and high BP), 20 patients with essential hypertension (HTN) (average aldosterone and high BP), 20 patients with secondary aldosteronism due to Bartter/Gitelman (BG) syndrome (high aldosterone and normal BP), and 20 healthy subjects (HS) (normal aldosterone and normal BP). Participants in each group were of similar age and sex distributions, and asymptomatic. Cardiac magnetic resonance including cine and T1 mapping was performed blind to the study group to quantify global LV mass index, as well as intracellular mass index and extracellular mass index considered as a measure of myocardial fibrosis in vivo.ResultsMedian plasma aldosterone concentration was as follows: PA = 709 pmol/l (interquartile range [IQR]: 430 to 918 pmol/l); HTN = 197 pmol/l (IQR: 121 to 345 pmol/l); BG = 297 pmol/l (IQR: 180 to 428 pmol/l); and HS = 105 pmol/l (IQR: 85 to 227 pmol/l). Systolic BP was as follows: PA = 147 ± 15 mm Hg; HTN = 133 ± 19 mm Hg; BG = 116 ± 9 mm Hg; and HS = 117 ± 12 mm Hg. LV end-diastolic volume showed underloading in BG and overloading in patients with PA (63 ± 13 ml/m² vs. 82 ± 15 ml/m²; p < 0.0001). Intracellular mass index increased with BP across groups (BG: 36 [IQR: 29 to 41]; HS: 40 [IQR: 36 to 46]; HTN: 51 [IQR: 42 to 54]; PA: 50 [IQR: 46 to 67]; p < 0.0001). Extracellular mass index was similar in BG, HS, and HTN (16 [IQR: 12 to 20]; 15 [IQR: 11 to 18]; and 14 [IQR: 12 to 17], respectively) but 30% higher in PA (21 [IQR: 18 to 29]; p < 0.0001) remaining significant after adjustment for mean BP.ConclusionsOnly primary pathological aldosterone excess combined with high BP increased both extracellular myocardial matrix and intracellular mass. Secondary aldosterone excess with normal BP did not affect extracellular myocardial matrix. (Study of Myocardial Interstitial Fibrosis in Hyperaldosteronism; NCT02938910).     

Outcomes of Prosthesis-Patient Mismatch Following Supra-Annular Transcatheter Aortic Valve Replacement: From the STS/ACC TVT Registry

ObjectivesThe aim of this study was to assess the outcomes of severe prosthesis-patient mismatch (PPM) in the TVT (Transcatheter Valve Therapy) Registry in patients undergoing supra-annular transcatheter aortic valve replacement (TAVR) for de novo stenosis or failed surgical bioprostheses (transcatheter aortic valve [TAV]–in–surgical aortic valve [SAV]).BackgroundSevere PPM has been associated with adverse outcomes following TAVR, yet the clinical outcome of severe PPM after supra-annular TAVR is largely unknown.MethodsSupra-annular TAVR was performed in patients enrolled in the TVT Registry with de novo stenosis (n = 42,174) or TAV-in-SAV (n = 5,446). Valve Academic Research Consortium-3 criteria were used to define severe PPM. The clinical impact of severe PPM on 1-year mortality and valve-related readmission was assessed using multivariate regression. A generalized linear mixed model was used to evaluate predictors of severe PPM.ResultsSevere PPM was found in 5.3% of patients undergoing de novo TAVR and 27.0% of patients undergoing TAV-in-SAV. The presence of severe PPM was not significantly associated with 1-year mortality or valve-related readmissions in both groups. Mean aortic gradients were higher in patients with severe PPM than in those without severe PPM at 1 month (9.7 ± 5.7 mm Hg vs. 7.3 ± 4.0 mm Hg; p < 0.001) and 1 year (10.2 ± 6.4 mm Hg vs. 8.0 ± 4.3 mm Hg; p < 0.001). Pre-procedural factors, including a <20-mm aortic annulus, were positive predictors of severe PPM in patients undergoing de novo TAVR (area under the curve = 0.795) and TAV-in-SAV (area under the curve = 0.764).ConclusionsSevere PPM after supra-annular TAVR was not associated with increased 1-year mortality or valve-related readmissions. Longer-term follow-up is needed to determine if higher residual gradients in patients with severe PPM predict long-term outcomes. (STS/ACC Transcatheter Valve Therapy Registry [TVT Registry]; NCT01737528)     

Utility of E/e′ Ratio During Low-Level Exercise to Diagnose Heart Failure With Preserved Ejection Fraction

BackgroundE/e′ ratio during exercise is the key parameter in identifying elevated pulmonary capillary wedge pressure (PCWP), and thus heart failure with preserved ejection fraction (HFpEF). However, its diagnostic value is limited when mitral inflow or tissue velocities are fused during elevated heart rate.ObjectivesThe authors hypothesized that E/e‘ ratio during low-level (20 W) exercise (E/e′_20W) can help diagnose HFpEF.MethodsErgometric exercise stress echocardiography was performed in 215 dyspneic patients with an EF ≥50%. The authors determined the feasibility of E/e′ ratio at each stage (frequency of patients who had measurable E/e′ without E-A fusion among 215 participants) and examined whether E/e′_20W could predict normal E/e′ ratio during peak exercise (E/e′_peak ≤15). The authors also evaluated whether E/e′_20W could predict normal PCWP during exercise (PCWP <25 mm Hg) in a subset of participants (n = 45) who underwent exercise right heart catheterization.ResultsThe feasibility of the E/e′ ratio decreased from 100% at rest to 96.3% during 20-W exercise and 74.9% during peak exercise caused by E-A fusion. In patients with E/e′_peak >15, there was an increase in E/e′ ratio from rest to 20-W exercise (11.2 ± 2.1 to 16.3 ± 3.5; P < 0.0001), but it did not change significantly from 20-W exercise to peak exercise (P = 0.12). E/e′_20W predicted E/e′_peak ≤15 (AUC: 0.91; P < 0.0001) with the cutoff value of ≤12.4 showing high specificity (94%) and positive predictive value (98%). During 20-W exercise, 93% of the HFpEF patients developed PCWP ≥25 mm Hg. E/e′_20W predicted normal PCWP during exercise (AUC: 0.77; P = 0.01) with the cutoff value of ≤12.4 showing high specificity (83%).ConclusionsE/e′ ratio during low-level exercise is highly feasible and predicts normal E/e′ ratio or PCWP during peak exercise with high specificity. These data suggest that E/e′_20W could be used as an alternative to the peak exercise value to rule out HFpEF in patients with dyspnea.     

12-Month Results From the Unblinded Phase of the RADIANCE-HTN SOLO Trial of Ultrasound Renal Denervation

ObjectivesThis study reports the 12-month results of the RADIANCE-HTN (A Study of the ReCor Medical Paradise System in Clinical Hypertension) SOLO trial following unblinding of patients at 6 months.BackgroundThe blood pressure (BP)–lowering efficacy and safety of endovascular ultrasound renal denervation (RDN) in the absence (2 months) and presence (6 months) of antihypertensive medications were previously reported.MethodsPatients with daytime ambulatory BP ≥135/85 mm Hg after 4 weeks off medication were randomized to RDN (n = 74) or sham (n = 72) and maintained off medication for 2 months. A standardized medication escalation protocol was instituted between 2 and 5 months (blinded phase). Between 6 and 12 months (unblinded phase), patients received antihypertensive medications at physicians’ discretion. Outcomes at 12 months included medication burden, change in daytime ambulatory systolic BP (dASBP) and office or home systolic BP (SBP), visit-to-visit variability in SBP, and safety.ResultsSixty-five of 74 RDN patients and 67 of 72 sham patients had 12-month dASBP measurements. The proportion of patients on ≥2 medications (27.7% vs. 44.8%; p = 0.041), the number of medications (1.0 vs. 1.4; p = 0.015), and defined daily dose (1.4 vs. 2.2; p = 0.007) were less with RDN versus sham. The decrease in dASBP from baseline in the RDN group (−16.5 ± 12.9 mm Hg) remained stable at 12 months. The RDN versus sham adjusted difference at 12 months was −2.3 mm Hg (95% confidence interval [CI]: −5.9 to 1.3 mm Hg; p = 0.201) for dASBP, −6.3 mm Hg (95% CI: −11.1 to −1.5 mm Hg; p = 0.010) for office SBP, and −3.4 mm Hg (95% CI: −6.9 to 0.1 mm Hg; p = 0.062) for home SBP. Visit-to-visit variability in SBP was smaller in the RDN group. No renal artery injury was detected on computed tomographic or magnetic resonance angiography.ConclusionsDespite unblinding, the BP-lowering effect of RDN was maintained at 12 months with fewer prescribed medications compared with sham.     

Prognostic Implications of Left Atrial Stiffness Index in Heart Failure Patients With Preserved Ejection Fraction

BackgroundThe left atrium (LA) plays an important role in the pathophysiology and disease progression of heart failure with preserved ejection fraction (HFpEF).ObjectivesThis study sought to assess the prognostic potential of LA stiffness index in patients who have HFpEF.MethodsThis study retrospectively screened patients with elevated left ventricular end-diastolic pressure (≥16 mm Hg) and preserved ejection fraction (≥50%) between January 1, 2004, and December 31, 2019. All patients underwent left heart catheterization to measure left ventricular end-diastolic pressure. Among these, 307 patients who had suitable image quality for left peak atrial longitudinal strain (PALS) measurement were analyzed. The study population was classified into low LA stiffness (n = 178, early diastolic transmitral inflow velocity/mitral annulus early diastolic velocity [E/e′]/PALS ≤0.26) and high LA stiffness (n = 129, E/e′/PALS >0.26) according to the best LA stiffness index (E/e′/PALS) cutoff value. The primary outcome was a composite of mortality or hospitalization caused by heart failure during follow-up.ResultsLA stiffness index showed good correlations with E/e′ (r = 0.737; P < 0.001), LA volume index (r = 0.529; P < 0.001), right ventricular systolic pressure (r = 0.404; P < 0.001), and log N-terminal pro–B-type natriuretic peptide (r = 0.540; P < 0.001). LA stiffness index demonstrated better predictive performance than echocardiographic diastolic parameters did (P < 0.001). Patients with low LA stiffness had better clinical outcomes than those with high LA stiffness during a median follow-up of 6 years did (P < 0.001). In multivariable analysis, LA stiffness index was independently associated with increased risk of the composite endpoint of death or heart failure hospitalization (HR: 1.59 [95% CI: 1.01-2.51]; P = 0.044).ConclusionsIncreased LA stiffness was associated with increased risk for all-cause mortality and hospitalization caused by heart failure in patients who have HFpEF, and its prognostic role was more pronounced than that of indexes of left ventricular filling pressure.     

Outcomes of Redo Transcatheter Aortic Valve Replacement According to the Initial and Subsequent Valve Type

BackgroundAs transcatheter aortic valve (TAV) replacement is increasingly used in patients with longer life expectancy, a sizable proportion will require redo TAV replacement (TAVR). The unique configuration of balloon-expandable TAV (bTAV) vs a self-expanding TAV (sTAV) potentially affects TAV-in-TAV outcome.ObjectivesThe purpose of this study was to better inform prosthesis selection, TAV-in-TAV outcomes were assessed according to the type of initial and subsequent TAV.MethodsPatients from the Redo-TAVR registry were analyzed using propensity weighting according to their initial valve type (bTAV [n = 115] vs sTAV [n = 106]) and subsequent valve type (bTAV [n = 130] vs sTAV [n = 91]).ResultsPatients with failed bTAVs presented later (vs sTAV) (4.9 ± 2.1 years vs 3.7 ± 2.3 years; P < 0.001), with smaller effective orifice area (1.0 ± 0.7 cm² vs 1.3 ± 0.8 cm²; P = 0.018) and less frequent dominant regurgitation (16.2% vs 47.3%; P < 0.001). Mortality at 30 days was 2.3% (TAV-in-bTAV) vs 0% (TAV-in-sTAV) (P = 0.499) and 1.7% (bTAV-in-TAV) vs 1.0% (sTAV-in-TAV) (P = 0.612); procedural safety was 72.6% (TAV-in-bTAV) vs 71.2% (TAV-in-sTAV) (P = 0.817) and 73.2% (bTAV-in-TAV) vs 76.5% (sTAV-in-TAV) (P = 0.590). Device success was similar according to initial valve type but higher with subsequent sTAV vs bTAV (77.2% vs 64.3%; P = 0.045), primarily because of lower residual gradients (10.3 mm Hg [8.9-11.7 mm Hg] vs 15.2 mm Hg [13.2-17.1 mm Hg]; P < 0.001). Residual regurgitation (moderate or greater) was similar after bTAV-in-TAV and sTAV-in-TAV (5.7%) and nominally higher after TAV-in-bTAV (9.1%) vs TAV-in-sTAV (4.4%) (P = 0.176).ConclusionsIn selected patients, no association was observed between TAV type and redo TAVR safety or mortality, yet subsequent sTAV was associated with higher device success because of lower redo gradients. These findings are preliminary, and more data are needed to guide valve choice for redo TAVR.     

Transvalvular Pressure Gradients and All-Cause Mortality Following TAVR: A Multicenter Echocardiographic and Invasive Registry

BackgroundLow ejection fraction (EF) and low flow as determined by an echocardiographic stroke volume index (SVi) <35 mL/m² are associated with low transvalvular gradients and increased mortality in both severe aortic stenosis (AS) and post–transcatheter aortic valve replacement (TAVR). Absence of an elevated echocardiographic transaortic gradient post-TAVR is considered a marker of procedural success despite the absence of data on its impact on mortality.ObjectivesThe authors sought to examine the association of invasive and echocardiographic gradients post-TAVR with all-cause mortality in relation to flow and EF.MethodsIn a multicenter retrospective registry of patients undergoing TAVR, Cox models with regression splines explored the relationship between invasive and echocardiographic gradients post-TAVR with 2-year mortality. An invasive gradient <5 mm Hg was considered low, between ≥5 and <10 mm Hg was considered intermediate, and ≥10 mm Hg was considered high. An echocardiographic gradient <10 mm Hg was considered low, ≥10 and <20 mm Hg was considered intermediate, and ≥20 mm Hg was considered high.ResultsHigher mortality occurred in low echocardiographic gradients at discharge relative to intermediate gradients (P < 0.001), and low gradient was associated with lower EF and echocardiographic SVi (P < 0.001 and P < 0.008, respectively). Lower mortality occurred in low invasive gradients relative to intermediate gradients (P = 0.012) with no difference in EF and echocardiographic SVi between groups (P = 0.089 and P = 0.947, respectively). There were insufficient observations to determine the impact of high echocardiographic and invasive gradients on mortality.ConclusionsIn this large retrospective analysis, the impact of transaortic gradients on mortality after TAVR was not linear and complex, showing opposite results among echocardiographic and invasive measurements in low-gradient patients.