Abstract
Aims
Patients with pulmonary hypertension (PHT) are often excluded from surgical therapies for tricuspid regurgitation (TR). Transcatheter tricuspid valve repair (TTVR) with the MitraClip™ ...technique is a novel treatment option for these patients. We aimed to assess the role of PHT in severe TR and its implications for TTVR.
Methods and results
A total of 243 patients underwent TTVR at two centres. One hundred twenty-one patients were grouped as iPHT+ invasive systolic pulmonary artery pressures (PAPs) ≥50 mmHg. Patients were similarly stratified according to echocardiographic PAPs (ePHT). The occurrence of the combined clinical endpoint (death, heart failure hospitalization, and reintervention) was investigated during a follow-up of 330 (interquartile range 175–402) days. iPHT+ patients were at higher preoperative risk (P < 0.01), had more severe symptoms (P = 0.01), higher N-terminal pro-B-type natriuretic peptide levels (P < 0.01), more impaired right ventricular (RV) function (P < 0.01), and afterload corrected RV function (P < 0.01). Procedural TTVR success was similar in iPHT+ and iPHT− patients (84 vs. 84%, P = 0.99). The echocardiographic diagnostic accuracy to detect iPHT was only 55%. During follow-up, 35% of patients reached the combined clinical endpoint. The discordant diagnosis of iPHT+/ePHT− carried the highest risk for the combined clinical endpoint HR 3.76 (CI 2.25–6.37), P < 0.01, while iPHT+/ePHT+ patients had a similar survival-free time from the combined endpoint compared to iPHT− patients (P = 0.48). In patients with isolated tricuspid procedure (n = 131) a discordant iPHT+/ePHT− diagnosis and an impaired afterload corrected RV function (P < 0.01 for both) were independent predictors for the occurrence of the combined endpoint.
Conclusion
The discordant echocardiographic and invasive diagnosis of PHT in severe TR predicts outcomes after TTVR.
Tricuspid regurgitation is associated with increased rates of heart failure (HF) and mortality. Transcatheter tricuspid valve interventions (TTVI) are promising, but the clinical benefit is unknown.
...The purpose of this study was to investigate the potential benefit of TTVI over medical therapy in a propensity score matched population.
The TriValve (Transcatheter Tricuspid Valve Therapies) registry collected 472 patients from 22 European and North American centers who underwent TTVI from 2016 to 2018. A control cohort formed by 2 large retrospective registries enrolling medically managed patients with ≥ moderate tricuspid regurgitation in Europe and North America (n = 1,179) were propensity score 1:1 matched (distance ± 0.2 SD) using age, EuroSCORE II, and systolic pulmonary artery pressure. Survival was tested with Cox regression analysis. Primary endpoint was 1-year mortality or HF rehospitalization or the composite.
After matching, 268 adequately matched pairs of patients were identified. Compared with control subjects, TTVI patients had lower 1-year mortality (23 ± 3% vs. 36 ± 3%; p = 0.001), rehospitalization (26 ± 3% vs. 47 ± 3%; p < 0.0001), and composite endpoint (32 ± 4% vs. 49 ± 3%; p = 0.0003). TTVI was associated with greater survival and freedom from HF rehospitalization (hazard ratio HR: 0.60; 95% confidence interval CI: 0.46 to 0.79; p = 0.003 unadjusted), which remained significant after adjusting for sex, New York Heart Association functional class, right ventricular dysfunction, and atrial fibrillation (HR: 0.39; 95% CI: 0.26 to 0.59; p < 0.0001) and after further adjustment for mitral regurgitation and pacemaker/defibrillator (HR: 0.35; 95% CI: 0.23 to 0.54; p < 0.0001).
In this propensity-matched case-control study, TTVI is associated with greater survival and reduced HF rehospitalization compared with medical therapy alone. Randomized trials should be performed to confirm these results.
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This study investigated patterns of right ventricular (RV) contraction by using cardiac magnetic resonance (CMR) imaging in patients undergoing transcatheter tricuspid valve repair (TTVR).
The role ...of RV function in patients with severe tricuspid regurgitation undergoing TTVR is poorly understood.
Global RV dysfunction was defined as CMR-derived RV ejection fraction (RVEF) ≤45% and longitudinal RV dysfunction was defined as tricuspid annular plane systolic excursion (TAPSE) <17 mm on echocardiography. Patients were stratified into 3 types of RV contraction: type I, TAPSE ≥17 and RVEF >45%; type II, TAPSE <17 and RVEF >45%; and type III, TAPSE <17 and RVEF ≤45%. CMR feature tracking was performed to assess longitudinal and circumferential RV strain. The primary outcome was a composite of all-cause mortality or first heart failure hospitalization.
Of 79 patients (median age 79 years, 51% female), 18 (23%) presented with global and 40 (51%) presented with longitudinal RV dysfunction. The composite outcome occurred in 22 patients (median follow-up 362 days). Global RV dysfunction but not longitudinal RV dysfunction (hazard ratio: 6.62; 95% confidence interval: 2.77-15.77; and hazard ratio: 1.30; 95% confidence interval: 0.55-3.08, respectively) was associated with the composite outcome. Compared with type I RV contraction, patients with type II RV contraction exhibited increased circumferential strain, with a preservation of RVEF despite diminished longitudinal strain. Patients with type III RV contraction exhibited both diminished longitudinal and circumferential strain, resulting in an impaired RVEF. Patients with type III RV contraction showed the worst survival (P < 0.001).
Global RV dysfunction is a predictor of outcomes among TTVR patients. Tricuspid regurgitation patients can be stratified into 3 types of RV contraction, in which a loss of longitudinal function can be compensated by increasing circumferential function, preserving RVEF and favorable outcomes.
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This study sought to examine the impact of chronic right ventricular (RV) volume overload and implications of tricuspid regurgitation (TR) reduction on biventricular function.
Severe TR is a major ...determinant of adverse outcomes in advanced heart failure patients. The understanding of TR pathophysiology and implications of correction is still limited. Transcatheter tricuspid edge-to-edge repair (TTVR) is a new treatment option in patients at high surgical risk and provides a unique pathophysiological model without confounding effects of cardiac surgery.
Twenty-nine patients (78 ± 4 years of age) with severe isolated TR and high surgical risk underwent TTVR using the MitraClip system, and of these 18 underwent repeated cardiac magnetic resonance. Clinical follow-up was realized at 1 and 6 months after the intervention.
TR fraction was reduced from 41% to 21% (p < 0.01) without increase in RV afterload (p = 0.52) and RV end-diastolic volume (p < 0.01), and RV stroke volume decreased (p = 0.03), whereas RV effective forward flow increased (p = 0.03). Left ventricular (LV) filling improved with an increase in LV end-diastolic volume (p = 0.01) and LV stroke volume (p = 0.02), leading to an augmentation of cardiac indices (2.2 ± 0.6 l/min/m2 vs. 2.7 ± 0.6 l/min/m2; p < 0.01) with similar results at 6 months follow-up. After TTVR, New York Heart Association functional class significantly improved (p < 0.01), peripheral edema decreased (p = 0.01), and 6-min walk distance increased by 20% and 22% after 1 and 6 months, respectively (p < 0.01).
TTVR reduces chronic RV volume overload without increase in RV afterload, improves RV performance and LV filling, and enhances cardiac output. These changes translate into symptomatic and functional improvement. These implications for biventricular physiology and clinical status are maintained at 6 months follow-up.
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Abstract Background Optimal patient characterization in heart failure with preserved ejection fraction (HFpEF) is essential to tailor successful treatment strategies. Cardiac magnetic resonance ...(CMR)–derived T1 mapping can noninvasively quantify diffuse myocardial fibrosis as extracellular volume fraction (ECV). Objectives This study aimed to elucidate the diagnostic performance of T1 mapping in HFpEF by examining the relationship between ECV and invasively measured parameters of diastolic function. It also investigated the potential of ECV to differentiate among pathomechanisms in HFpEF. Methods We performed T1 mapping in 24 patients with HFpEF and 12 patients without heart failure symptoms. Pressure-volume loops were obtained with a conductance catheter during basal conditions and handgrip exercise. Transient pre-load reduction was used to extrapolate the diastolic stiffness constant. Results Patients with HFpEF showed higher ECV (p < 0.01), elevated load-independent passive left ventricular (LV) stiffness constant (beta) (p < 0.001), and a longer time constant of active LV relaxation (p = 0.02). ECV correlated highly with beta (r = 0.75; p < 0.001). Within the HFpEF cohort, patients with ECV greater than the median showed a higher beta (p = 0.05), whereas ECV below the median identified patients with prolonged active LV relaxation (p = 0.01) and a marked hypertensive reaction to exercise due to pathologic arterial elastance (p = 0.04). On multiple linear regression analyses, ECV independently predicted intrinsic LV stiffness (β = 0.75; p < 0.01). Conclusions Diffuse myocardial fibrosis, assessed by CMR-derived T1 mapping, independently predicts invasively measured LV stiffness in HFpEF. Additionally, ECV helps to noninvasively distinguish the role of passive stiffness and hypertensive exercise response with impaired active relaxation. (Left Ventricular Stiffness vs. Fibrosis Quantification by T1 Mapping in Heart Failure With Preserved Ejection Fraction STIFFMAP; NCT02459626 )
The aims of the study were to assess the prognostic significance of cardiac magnetic resonance myocardial feature tracking (CMR-FT) in a large multicenter study and to evaluate the most potent CMR-FT ...predictor of hard clinical events following myocardial infarction (MI).
CMR-FT is a new method that allows accurate assessment of global and regional circumferential, radial, and longitudinal myocardial strain. The prognostic value of CMR-FT in patients with reperfused MI is unknown.
The study included 1,235 MI patients (n = 795 with ST-segment elevation MI and 440 with non–ST-elevation MI) at 15 centers. All patients were reperfused by primary percutaneous coronary intervention. Central core laboratory–masked analyses were performed to determine left ventricular (LV) circumferential, radial, and longitudinal strain. The primary clinical endpoint of the study was the occurrence of major adverse cardiac events within 12 months after infarction.
Patients with cardiovascular events had significantly impaired CMR-FT strain values (p < 0.001 for all). Global longitudinal strain was identified as the strongest CMR-FT parameter of future cardiovascular events and emerged as an independent predictor of poor prognosis following MI even after adjustment for established prognostic markers. Global longitudinal strain provided an incremental prognostic value for all-cause mortality above LV ejection fraction (c-index increase from 0.65 to 0.73; p = 0.04) and infarct size (c-index increase from 0.60 to 0.78; p = 0.002).
CMR-FT is a superior measure of LV function and performance early after reperfused MI with incremental prognostic value for mortality over and above LV ejection fraction and infarct size. (Abciximab i.v. Versus i.c. in ST-segment elevation Myocardial Infarction AIDA STEMI; NCT00712101; Thrombus Aspiration in ThrOmbus Containing culpRIT Lesions in Non-ST-Elevation Myocardial Infarction TATORT-NSTEMI; NCT01612312)
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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.
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.
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 (
=0.019) and end-systolic volumes (
=0.001) than the LVEF 50% to 60% cohort; stroke volume (
=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;
=0.018). Pressure-volume loop analyses demonstrated higher baseline LV contractility (end-systolic elastance, 1.85 vs 1.33 mm Hg/mL;
<0.001) and passive diastolic stiffness (β constant, 0.032 versus 0.018;
=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;
=0.005). During handgrip exercise, patients with LVEF >60% had higher increases in end-systolic elastance (1.85 versus 0.82 mm Hg/mL;
=0.023), attenuated increases in indexed end-systolic volume (-1 versus 7 mL/m²;
<0.004), and more exaggerated increases in LV filling pressures (8 vs 5 mm Hg;
=0.023). LV stroke volume decreased in the LVEF >60% cohort (
=0.007) under exertion.
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.
Graphical Abstract
Graphical Abstract
Proposed pathway after heart failure hospitalization. Top line shows risk of hospital readmission and mortality for short-, mid- and long-term follow-up. Middle ...line shows actions to be taken at specific time-points, especially early after hospital discharge. Bottom line gives information of patient groups needing special attention.
This study was designed to assess hemodynamic changes in response to transcatheter tricuspid valve edge-to-edge repair (TTVR) and to identify hemodynamic predictors associated with mortality.
Severe ...tricuspid regurgitation (TR) is associated with high mortality. TTVR effectively alleviates heart failure symptoms, but comprehensive hemodynamic characterization of patients undergoing TTVR is currently lacking.
This international, multicenter study included 236 patients undergoing TTVR. Data from clinical assessment, echocardiography, intraprocedural right heart catheterization, and noninvasive cardiac output measurement were analyzed. Hemodynamic predictors for mortality were identified using linear Cox regression analysis and were used for stratification of patients with subsequent analysis of survival time.
Patients (median age 78 years, 53% women) were symptomatic (89% in New York Heart Association functional class III or IV) because of severe TR (grade ≥3+ in 100%). TTVR significantly reduced TR at discharge (grade ≥3+ in 16%; p < 0.001), with a corresponding 19% reduction of the right atrial v wave (21 mm Hg vs. 16 mm Hg; p < 0.001) and an improvement in cardiac output (from 3.5 to 4.0 l/min; p < 0.01). Invasive mean pulmonary artery pressure, transpulmonary gradient, pulmonary vascular resistance, and right ventricular stroke work were significant predictors of 1-year mortality (p < 0.05 for all). Hemodynamic stratification by mean pulmonary artery pressure and transpulmonary gradient best predicted 1-year survival (p < 0.001). Although patients with pre-capillary dominant pulmonary hypertension showed an unfavorable prognosis (1-year survival 38%), patients without or with post-capillary pulmonary hypertension had favorable outcome (1-year survival 92% or 78%, respectively).
Invasive assessment of cardiopulmonary hemodynamic status predicts survival after TTVR. Invasive hemodynamic characterization may help identify patients profiting most from TTVR.
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BACKGROUND:Both radiofrequency and ultrasound endovascular renal sympathetic denervation (RDN) have proven clinical efficacy for the treatment of hypertension. We performed a head-to-head comparison ...of these technologies.
METHODS:Patients with resistant hypertension were randomly assigned in a 1:1:1 manner to receive either treatment with (1) radiofrequency RDN of the main renal arteries; (2) radiofrequency RDN of the main renal arteries, side branches, and accessories; or (3) an endovascular ultrasound–based RDN of the main renal artery. The primary end point was change in systolic daytime ambulatory blood pressure at 3 months.
RESULTS:Between June 2015 and June 2018, 120 patients were enrolled (mean age, 64±9 years±SD; mean daytime blood pressure, 153/86±12/13 mm Hg). Of these, 39 were randomly assigned to radiofrequency main renal artery ablation, 39 to combined radiofrequency ablation of the main artery and branches, and 42 to ultrasound-based treatment. Baseline daytime blood pressure, clinical characteristics, and treatment were well balanced between the groups. At 3 months, systolic daytime ambulatory blood pressure decreased by 9.5±12.3 mm Hg (P<0.001) in the whole cohort. Although blood pressure was significantly more reduced in the ultrasound ablation group than in the radiofrequency ablation group of the main renal artery (–13.2±13.7 versus –6.5±10.3 mm Hg; mean difference, –6.7 mm Hg; global P=0.038 by ANOVA, adjusted P=0.043), no significant difference was found between the radiofrequency ablation groups (–8.3±11.7 mm Hg for additional side branch ablation; mean difference, –1.8 mm Hg; adjusted P>0.99). Similarly, the blood pressure reduction was not found to be significantly different between the ultrasound and the side branch ablation groups. Frequencies of blood pressure response ≥5 mm Hg were not significantly different (global P=0.77).
CONCLUSIONS:In patients with resistant hypertension, endovascular ultrasound–based RDN was found to be superior to radiofrequency ablation of the main renal arteries only, whereas a combined approach of radiofrequency ablation of the main arteries, accessories, and side branches was not.
CLINICAL TRIAL REGISTRATION:URLhttps://www.clinicaltrials.gov. Unique identifierNCT02920034.
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