Quantifying Benefit-Risk Preferences for Heart Failure Devices: A Stated-Preference Study

Background: Regulatory and clinical decisions involving health technologies require judgements about relative importance of their expected benefits and risks. We sought to quantify heart-failure patients’ acceptance of therapeutic risks in exchange for improved effectiveness with implantable devices. Methods: Individuals with heart failure recruited from a national web panel or academic medical center completed a web-based discrete-choice experiment survey in which they were randomized to one of 40 blocks of 8 experimentally controlled choice questions comprised of 2 device scenarios and a no-device scenario. Device scenarios offered an additional year of physical functioning equivalent to New York Heart Association class III or a year with improved (ie, class II) symptoms, or both, with 30-day mortality risks ranging from 0% to 15%, in-hospital complication risks ranging from 0% to 40%, and a remote adjustment device feature. Logit-based regression models fit participants’ choices as a function of health outcomes, risks and remote adjustment. Results: Latent-class analysis of 613 participants (mean age, 65; 49% female) revealed that two-thirds were best represented by a pro-device, more risk-tolerant class, accepting up to 9% (95% CI, 7%–11%) absolute risk of device-associated mortality for a one-year gain in improved functioning (New York Heart Association class II). Approximately 20% were best represented by a less risk-tolerant class, accepting a maximum device-associated mortality risk of 3% (95% CI, 1%–4%) for the same benefit. The remaining class had strong antidevice preferences, thus maximum-acceptable risk was not calculated. Conclusions: Quantitative evidence on benefit-risk tradeoffs for implantable heart-failure device profiles may facilitate incorporating patients’ views during product development, regulatory decision-making, and clinical practice.

Transcatheter tricuspid valve repair: early experience in the Netherlands

Background Symptomatic tricuspid regurgitation (TR) is increasingly prevalent and impairs quality of life and survival, despite medical treatment. Transcatheter tricuspid valve repair (TTVR) has recently become available as a treatment option for patients not eligible for tricuspid valve surgery. In this study we describe the early experience with TTVR in the Netherlands. Methods All consecutive patients scheduled for TTVR in two tertiary hospitals were included in the current study. Patients were symptomatic and had severe functional TR. TTVR was performed either with the MitraClip (off-label use) or dedicated TriClip delivery system and device. Procedural success was defined as achievement of clip implantation, TR reduction ≥ 1 grade and no need for re-do surgical or transcatheter intervention. Clinical improvement was evaluated after 4 weeks. Results Twenty-one patients (median age 78 years, 33% male, 95% New York Heart Association class ≥ 3, 100% history of atrial fibrillation) underwent TTVR. Procedural success was achieved in 16 patients, of whom 15 reported symptomatic improvement (New York Heart Association class 1 or 2). There was no in-hospital mortality and no major complications occurred. Baseline glomerular filtration rate and TR coaptation gap size were associated with procedural success. Conclusion The current study showed that TTVR seems a promising treatment option for patients with severe functional TR deemed high risk for surgery. Successful TR reduction is most likely in patients with limited coaptation gap size and strongly determines clinical benefit. Adequate patient selection and timing of treatment seem essential for an optimal patient outcome.

Evaluation of the effectiveness of a phase three specialised heart failure cardiac rehabilitation programme on cardiovascular risk factor profile

Background/Aims Cardiac rehabilitation has long been seen as effective for many cardiovascular diseases and, more recently, as having a positive impact on patients with heart failure. To evaluative the effectiveness of a phase three specialised heart failure cardiac rehabilitation programme on patients' cardiovascular risk factor profile. Methods This retrospective, longitudinal study examined profile factors of patients, pre- and post-cardiac rehabilitation programme. Patients with New York Heart Association class I–III, of any origin, were recruited through a specialised heart failure service to a 10-week exercise and education programme. Outcome variables included anxiety, depression, quality of life (Minnesota), 6-minute walking test result, blood pressure, weight, waist circumference, body mass index, Duke Activity Status Index and self-care, and were analysed with the Statistical Package for the Social Sciences using repeated measures t-test. Results 100 patients were eligible and 85 patients completed the programmes. Mean age was 66 years, 80% male, 59% were New York Heart Association class I and 73% had ejection fraction of ≤40%. There was a significant improvement in 6-minute walking test, systolic blood pressure, quality of life and anxiety post programme. Conclusions In-hospital and out of hospital cardiac care has developed significantly, especially in acute symptom control. More recently, emphasis has been put on the long-term control of other risk factors. This study contributes to the literature indicating that attendance at a hospital-based phase three cardiac rehabilitation programme providing supervised, tailored exercise, with intensive education and psychological support, is effective in reducing risk factors and improving quality of life in patients with lower grades of heart failure.

Exercise Hemodynamic Profiling Is Associated With Outcome in Patients Undergoing Percutaneous Mitral Valve Repair

Background: Percutaneous mitral valve repair (PMVR) in high-risk patients is currently controversial, especially in those with secondary mitral regurgitation (MR). Exercise pulmonary hemodynamics may help to unmask cardiac dysfunction as well as the dynamic impact of MR. The present study sought to explore the clinical impact of preprocedural exercise right heart catheterization (RHC) for the selection of patients who could most benefit from PMVR. Methods: Sixty-eight patients with symptomatic primary and secondary MR and exercise RHC before PMVR were included in this retrospective analysis of the association of exercise RHC parameters with survival and improvement in New York Heart Association class within 12 months. Results: Median patient age was 77 years (±8.5), 37% were female, and 81% presented with New York Heart Association class III. A total of 65% of the patients had left ventricular ejection fraction <55%. MR was severe in 49% and moderate-to-severe in 51%. Twenty-two patients (32%) died within the follow-up period of 19 months (interquartile range, 9–32); they had a lower rise (Δ) in the V-wave on pulmonary artery wedge pressure tracings. Patients with ΔV-wave ≥17 mm Hg had a reduced risk of death after PMVR (hazard ratio, 0.11 [95% CI, 0.04–0.33], P <0.001), independent of age, frailty index, and workload during RHC. A higher ΔV-wave was also associated with New York Heart Association improvement (odds ratio, 1.14 [95% CI, 1.07–1.24]; P <0.001), and 79% of patients with ∆V-wave ≥15 mm Hg were in New York Heart Association class I or II at follow-up (<15 mm Hg: 28%). These results were for the most part confirmed in the subgroup of patients with secondary MR (65%). Conclusions: In our cohort of patients with indication for PMVR, preprocedural exercise RHC was able to identify patients with an unfavorable outcome. Further studies with larger patient numbers are warranted before this approach can be implemented in a structured diagnostic workup of patients under evaluation for PMVR.

Transcatheter Treatment of Secondary Tricuspid Regurgitation With Direct Annuloplasty

Background: Treatment options for secondary tricuspid regurgitation (TR) remain limited. Early real-world data of a new percutaneous direct annuloplasty system for tricuspid repair were examined. Methods: The first 60 patients treated with the Cardioband tricuspid valve repair system at 4 centers were included in this retrospective study. The primary efficacy end point was technical success with reduction of TR ≥2 grades at discharge. Combined primary safety end point was major adverse events (death, myocardial infarction, cardiothoracic surgery, and stroke) at 30 days. Results: Median patient age was 76 years (73–82), median EuroScore II was 3.9% (2.2–8.1), heart failure with preserved ejection fraction was present in 78%, and 81.7% were in the New York Heart Association class III/IV. Massive or torrential TR was found in 51.7%, and severe TR in 48.3%. The primary efficacy end point was achieved in 45%, while 60.3% of patients had less-than-severe TR at discharge. Vena contracta was reduced by 47% from 12.9±4.8 to 7.0±3.4 mm ( P <0.001). Overall, the majority of patients (81.7%) improved at least by 1 New York Heart Association class. At follow-up 81.3% of patients presented in the New York Heart Association class I or II. The primary safety end point occurred in 4 patients with 2 in-hospital deaths, both not device related. Right coronary artery complications (vessel perforation or stent implantation) occurred in 9 patients (15%). Procedural time decreased from 298 to 185 minutes ( P <0.001) with efficacy remaining stable ( P =0.817) when comparing procedure numbers 11 or more to the earliest 5 procedures per center. Conclusions: This first real-world experience suggests that transcatheter treatment of advanced secondary TR using direct annuloplasty is feasible and reasonably safe early in the learning curve, with significant symptomatic benefit. Further studies are warranted to provide data on long-term outcome and patient prognosis.

Clinical Outcomes of Autologous Stem Cell–Patch Implantation for Patients With Heart Failure With Nonischemic Dilated Cardiomyopathy

Background Clinical effectiveness of autologous skeletal cell‐patch implantation for nonischemic dilated cardiomyopathy has not been clearly elucidated in clinical settings. This clinical study aimed to determine the feasibility, safety, therapeutic efficacy, and the predictor of responders of this treatment in patients with nonischemic dilated cardiomyopathy. Methods and Results Twenty‐four nonischemic dilated cardiomyopathy patients with left ventricular ejection fraction <35% on optimal medical therapy were enrolled. Autologous cell patches were implanted over the surface of the left ventricle through left minithoracotomy without procedure‐related complications and lethal arrhythmia. We identified 13 responders and 11 nonresponders using the combined indicator of a major cardiac adverse event and incidence of heart failure event. In the responders, symptoms, exercise capacity, and cardiac performance were improved postoperatively (New York Heart Association class II 7 [54%] and III 6 [46%] to New York Heart Association class II 12 [92%] and I 1 [8%], P <0.05, 6‐minute walk test; 471 m [370–541 m] to 525 m [425–555 m], P <0.05, left ventricular stroke work index; 31.1 g·m 2 ·beat [22.7–35.5 g·m 2 ·beat] to 32.8 g·m 2 ·beat [28–38.5 g·m 2 ·beat], P =0.21). However, such improvement was not observed in the nonresponders. In responders, the actuarial survival rate was 90.9±8.7% at 5 years, which was superior to the estimated survival rate of 70.9±5.4% using the Seattle Heart Failure Model. However, they were similar in nonresponders (47.7±21.6% and 56.3±8.1%, respectively). Multivariate regression model with B‐type natriuretic peptide, pulmonary capillary wedge pressure, and expression of histone H3K4me3 (H3 lysine 4 trimethylation) strongly predicted the responder of this treatment (B‐type natriuretic peptide: odds ratio [OR], 0.96; pulmonary capillary wedge pressure: ​OR, 0.58; H3K4me3: OR, 1.35, receiver operating characteristic–area under the curve, 0.96, P <0.001). Conclusions This clinical trial demonstrated that autologous skeletal stem cell–patch implantation might promise functional recovery and good clinical outcome in selected patients with nonischemic dilated cardiomyopathy, in addition to safety and feasibility. Registration URL: http://www.umin.ac.jp/english/ . Unique identifiers: UMIN000003273, UMIN0000012906 and UMIN000015892.

Transcatheter Aortic Valve Replacement for Degenerated Transcatheter Aortic Valves: The TRANSIT International Project

Background: Transcatheter aortic valve replacement (TAVR) has determined a paradigm shift in the treatment of patients with severe aortic stenosis. However, the durability of bioprostheses is still a matter of concern, and little is known about the management of degenerated TAV. We sought to evaluate the outcomes of patients with a degenerated TAV treated by means of a second TAVR. Methods: The TRANSIT is an international registry that included cases of degenerated TAVR from 28 centers. Among around 40 000 patients treated with TAVR in the participating centers, 172 underwent a second TAVR: 57 (33%) for a mainly stenotic degenerated TAV, 97 (56%) for a mainly regurgitant TAV, and 18 (11%) for a combined degeneration. Overall, the rate of New York Heart Association class III/IV at presentation was 73.5%. Results: Valve Academic Research Consortium 2 device success rate was 79%, as a consequence of residual gradient (14%) or regurgitation (7%). At 1 month, the overall mortality rate was 2.9%, while rates of new hospitalization and New York Heart Association class III/IV were 3.6% and 7%, respectively, without significant difference across the groups. At 1 year, the overall mortality rate was 10%, while rates of new hospitalization and New York Heart Association class III/IV were 7.6% and 5.8%, respectively, without significant difference across the groups. No cases of valve thrombosis were recorded. Conclusions: Selected patients with a degenerated TAV may be safely and successfully treated by means of a second TAVR. This finding is of crucial importance for the adoption of the TAVR technology in a lower risk and younger population. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04500964.

Levels of Trimethylamine N-Oxide Remain Elevated Long Term After Left Ventricular Assist Device and Heart Transplantation and Are Independent From Measures of Inflammation and Gut Dysbiosis

Background: Trimethylamine N-oxide (TMAO)—a gut-derived metabolite—is elevated in heart failure (HF) and linked to poor prognosis. We investigated variations in TMAO in HF, left ventricular assist device (LVAD), and heart transplant (HT) and assessed its relation with inflammation, endotoxemia, oxidative stress, and gut dysbiosis. Methods: We enrolled 341 patients. TMAO, CRP (C-reactive protein), IL (interleukin)-6, TNF-α (tumor necrosis factor alpha), ET-1 (endothelin-1), adiponectin, lipopolysaccharide, soluble CD14, and isoprostane were measured in 611 blood samples in HF (New York Heart Association class I–IV) and at multiple time points post-LVAD and post-HT. Gut microbiota were assessed via 16S rRNA sequencing among 327 stool samples. Multivariable regression models were used to assess the relationship between TMAO and (1) New York Heart Association class; (2) pre- versus post-LVAD or post-HT; (3) biomarkers of inflammation, endotoxemia, oxidative stress, and microbial diversity. Results: ln-TMAO was lower among HF New York Heart Association class I (1.23 [95% CI, 0.52–1.94] µM) versus either class II, III, or IV (1.99 [95% CI, 1.68–2.30], 1.97 [95% CI, 1.71–2.24], and 2.09 [95% CI, 1.83–2.34] µM, respectively; all P <0.05). In comparison to class II–IV, ln-TMAO was lower 1 month post-LVAD (1.58 [95% CI, 1.32–1.83] µM) and 1 week and 1 month post-HT (0.97 [95% CI, 0.60–1.35] and 1.36 [95% CI, 1.01–1.70] µM). ln-TMAO levels in long-term LVAD (>6 months: 1.99 [95% CI, 1.76–2.22] µM) and HT (>6 months: 1.86 [95% CI, 1.66–2.05] µM) were not different from symptomatic HF. After multivariable adjustments, TMAO was not associated with biomarkers of inflammation, endotoxemia, oxidative stress, or microbial diversity. Conclusions: TMAO levels are increased in symptomatic HF patients and remain elevated long term after LVAD and HT. TMAO levels were independent from measures of inflammation, endotoxemia, oxidative stress, and gut dysbiosis.

Giving intravenous iron to patients with symptomatic heart failure is safe and cost effective

Aims/Background Heart failure affects approximately 1 million people in the UK, adversely affecting quality of life, functional capacity and cognitive health. Iron deficiency complicates heart failure in approximately 50% of patients. Giving intravenous ferric carboxymaltose has been shown to improve quality of life in patients with heart failure (New York Heart Association class and Kansas City Cardiomyopathy Questionnaire). Methods A quality improvement project was designed to assess the feasibility, safety and cost implications of establishing an intravenous iron service in the authors' centre. Results Between July and December 2019 61 patients who were screened met the inclusion criteria and were administered intravenous ferric carboxymaltose. There were statistically significant improvements in ferritin levels (83.3 ug/litre to 433 ug/litre; P<0.0001), transferrin saturation (18% to 30% P<0.0001) and haemoglobin levels (126 g/litre to 135 g/litre; P<0.01). No demonstrable changes in New York Heart Association class or quality of life scores were noted. The overall financial impact for the trust was income generation of £14 665, a net income of £240 per patient. Conclusions Intravenous iron replacement with ferric carboxymaltose is safe and cost effective, and should be considered in eligible iron-deficient patients with symptomatic heart failure. Integration with another day case intravenous service represented the most logistically simple and economically viable method of service delivery.