Therapy For Heart Failure Patients Research Articles

Guideline-Directed Therapy In An Elderly Homebound Population of Heart Failure Patients

Introduction Adherence to guideline-directed therapy in heart failure patients is an important goal. Traditionally, elderly patients have difficulties attaining target doses of these therapies and this may be exaggerated in a homebound population. Hypothesis We assessed the differences in use of Angiotensin-Converting Enzyme inhibitors (ACEis)/Angiotensin Receptor Blockers (ARBs) and Beta-Blockers (BBs) in homebound heart failure patients in 2 age groups (≥75 years old and Methods A total of 471 heart failure patients during January 2016-March 2020 were reviewed via electronic medical record (Refer to Table 1 for Characteristics). Homebound patients are characterized as those seen for medical visits at home or at a non-medical facility. Both groups were reviewed for the administration and dosage of ACEis/ARB and BBs. Due to the use of multiple ACEis and ARBs, daily doses were converted to a Lisinopril Equivalent Dose (LED) for a singular continuous variable for comparison. Similarly, beta-blocker daily dosages were converted to a Carvedilol Equivalent Dose (CED). Proportions of patients who reached target doses of Lisinopril (20-40 mg) and Carvedilol (25 mg BID) in both age groups were compared via t-test. Results Group 1 consisted of n=308 patients (65.4%). Group 2 consisted of n=163 patients (34.6%). Group 1 patients on ACEi/ARB and BB were 81.5% and 57.8%, respectively. Group 2 patients were on ACEi/ARB and BB at similar percentages (81.0% and 57.1%, respectively). Group 1 had a mean LED of 21.7±12.5 mg and a mean CED of 22.2±15.2 mg, with 49.0% reaching the target LED and 11.0% reaching the target CED. Group 2 had a mean LED of 23.2±12.5 mg and a mean CED of 24.5±17.6 mg, with 51.5% reaching the target LED and 12.9% reaching the target CED (Refer to Table 1). Both group means reached the target daily dose of Lisinopril (p=0.2440) but did not reach the minimum target daily dose of carvedilol (p=0.3087) (Refer to Figure 1). Conclusions Patients within both younger and older age demographics are able to reach similar daily doses of guideline-directed heart failure medication. Target doses of BBs were less frequently attained probably due to the frequent presence of numerous comorbidities.

Impact of Mitral Regurgitation Severity and Left Ventricular Remodeling on Outcome After MitraClip Implantation: Results From the Mitra-FR Trial

ObjectivesThis study aimed to identify a subset of patients based on echocardiographic parameters who might have benefited from transcatheter correction using the MitraClip system in the MITRA-FR (Percutaneous Repair with the MitraClip Device for Severe Functional/Secondary Mitral Regurgitation) trial. BackgroundIt has been suggested that differences in the degree of mitral regurgitation (MR) and left ventricular (LV) remodeling may explain the conflicting results between the MITRA-FR and the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation) trials. MethodsIn a post hoc analysis, we evaluated the interaction between the intervention and subsets of patients defined based on MR severity (effective regurgitant orifice [ERO], regurgitant volume [RVOL] and regurgitant fraction [RF]), LV remodeling (end-diastolic and end-systolic diameters and volumes) and combination of these parameters with respect to the composite of death from any cause or unplanned hospitalization for heart failure at 24 months. ResultsWe observed a neutral impact of the intervention in subsets with the highest MR degree (ERO ≥30 mm2, RVOL ≥45 ml or RF ≥50%) as in patients with milder MR degree. The same was seen in subsets with the milder LV remodeling using either diastolic or systolic diameters or volumes. When parameters of MR severity and LV remodeling were combined, there was still no benefit of the intervention including in the subset of patients with an ERO/end-diastolic volume ratio ≥ 0.15 despite similar ERO and LV end-diastolic volume compared with COAPT patients. ConclusionsIn the MITRA-FR trial, we could not identify a subset of patients defined based on the degree of the regurgitation, LV remodeling or on their combination, including those deemed as having disproportionate MR, that might have benefited from transcatheter correction using the MitraClip system. (Multicentre Study of Percutaneous Mitral Valve Repair MitraClip Device in Patients With Severe Secondary Mitral Regurgitation [MITRA-FR]; NCT01920698)

Impact of Tricuspid Regurgitation on Clinical Outcomes: The COAPT Trial

BackgroundThe presence of tricuspid regurgitation (TR) may affect prognosis in patients with mitral regurgitation (MR). ObjectivesThis study sought to determine the impact of TR on outcomes in patients with heart failure and severe secondary MR randomized to guideline-directed medical therapy (GDMT) or edge-to-edge repair with the MitraClip in the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) trial. MethodsA total of 614 patients with symptomatic heart failure with moderate to severe (3+) or severe (4+) secondary MR were randomized to maximally tolerated GDMT plus MitraClip or GDMT alone; 599 had core laboratory evaluable echocardiograms. Patients were divided into 2 groups by baseline TR severity: none/trace/mild TR (≤Mild TR) (n = 501 [83.6%]) and moderate/severe TR (≥Mod TR) (n = 98 [16.4%]). Two-year composite endpoints of death or heart failure hospitalization (HFH) and the individual endpoints were analyzed. ResultsPatients with ≥Mod TR were more likely to be New York Heart Association functional class III/IV (p < 0.0001) and have a Society of Thoracic Surgeons score of ≥8 (p < 0.0001), anemia (p = 0.02), chronic kidney disease (p = 0.003), and higher N-terminal pro–B-type natriuretic peptide (p = 0.02) than those with ≤Mild TR. Patients with ≥Mod TR had more severe MR (p = 0.0005) despite smaller left ventricular volumes (p = 0.005) and higher right ventricular systolic pressure (p < 0.0001). At 2 years, the composite rate of death or HFH was higher in patients with ≥Mod TR compared with ≤Mild TR treated with GDMT alone (83.0% vs. 64.3%; hazard ratio: 1.74; 95% confidence interval: 1.24 to 2.45; p = 0.001) but not following MitraClip (48.2% vs. 44.0%; hazard ratio: 1.14; 95% confidence interval: 0.71 to 1.84; p = 0.59). Rates of death or HFH, as well as death and HFH alone, were reduced by MitraClip compared with GDMT, irrespective of baseline TR grade (pinteraction = 0.16, 0.29, and 0.21 respectively). ConclusionsPatients with severe secondary MR who also had ≥Mod TR had worse clinical and echocardiographic characteristics and worse clinical outcomes compared to those with ≤Mild TR. Within the COAPT trial, MitraClip improved outcomes in patients with and without ≥Mod TR severity compared with GDMT alone. (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation [COAPT]; NCT01626079)

Predictors of Clinical Response to Transcatheter Reduction of Secondary Mitral Regurgitation: The COAPT Trial

BackgroundTranscatheter mitral valve repair with the MitraClip results in marked clinical improvement in some but not all patients with secondary mitral regurgitation (MR) and heart failure (HF). ObjectivesThis study sought to evaluate the clinical predictors of a major response to treatment in the COAPT trial. MethodsPatients with HF and severe MR who were symptomatic on maximally tolerated guideline-directed medical therapy (GDMT) were randomly assigned to MitraClip plus GDMT or GDMT alone. Super-responders were defined as those alive without HF hospitalization and with ≥20-point improvement in the Kansas City Cardiomyopathy Questionnaire overall summary (KCCQ-OS) score at 12 months. Responders were defined as those alive without HF hospitalization and with a 5 to <20-point KCCQ-OS improvement at 12 months. Nonresponders were those who either died, were hospitalized for HF, or had <5-point improvement in KCCQ-OS at 12 months. ResultsAmong 614 enrolled patients, 41 (6.7%) had missing KCCQ-OS data and could not be classified. At 12 months, there were 79 super-responders (27.2%), 55 responders (19.0%), and 156 nonresponders (53.8%) in the MitraClip arm compared with 29 super-responders (10.2%), 46 responders (16.3%), and 208 nonresponders (73.5%) in the GDMT-alone arm (overall p < 0.0001). Independent baseline predictors of clinical responder status were lower serum creatinine and KCCQ-OS scores and treatment assignment to MitraClip. MR grade and estimated right ventricular systolic pressure at 30 days were improved to a greater degree in super-responders and responders but not in nonresponders. ConclusionsBaseline predictors of clinical super-responders in patients with HF and severe secondary MR in the COAPT trial were lower serum creatinine, KCCQ-OS score and MitraClip treatment. Improved MR severity and reduced right ventricular systolic pressure at 30 days are associated with a long-term favorable clinical response after transcatheter mitral valve repair. (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation [COAPT]; NCT01626079)

Guideline-directed medical therapy in heart failure patients: impact of focused care provided by a heart failure clinic in comparison to general cardiology out-patient department

BackgroundThe usage of guideline-directed medical therapy (GDMT) in the treatment of heart failure (HF) has shown to reduce morbidity and mortality. However, majority of the HF patients do not receive GDMT or do not achieve the target dose. Literature has shown that the patients who are managed in HF clinics receive GDMT and target doses of disease-modifying drugs (DMD) when compared to those treated in other general cardiology outpatient departments (OPD’s). It was a retrospective hospital-based study in which patients treated in HF clinic and other cardiology OPD in the year of 2017 were included (200 patients in each arm). The aim of this study was to assess the impact of heart failure clinics in medication therapy management including usage of guideline-directed medical therapy, if target dose specified by the guideline is achieved and time to reach target dose in comparison to other general cardiology OPD’s. IRB and IEC approval were obtained before the commencement of the study. Data relevant to the study were obtained from the electronic medical record (EMR) and were compared between the study groups to see for the adherence to guideline and achievement of target doses. Data storage and analysis were performed using SPSS Version 24. A significance level of 5% was used.ResultsThe usage of GDMT was higher in HF clinic when compared to other cardiology OPD (81% vs 55%, P = 0.001). A significantly higher number of patients in HF clinic achieved target dose when compared to other cardiology OPD (58% vs 29% -betablockers, 45% vs 9% -ACEI/ARB/ARNI, P = 0.000). Moreover, the number of eligible patients receiving DMD was found to be higher in HF clinic (98% vs 85% -betablockers, 69% vs 44% -ACEI/ARB/ARNI, 76% vs 44% -MRA). Also, the patients in HF clinic attained the target doses faster when compared to other cardiology OPD. In addition, there was better improvement in ejection fraction, as well as decreased rate of rehospitalisation and mortality in patients managed in HF clinic.ConclusionHF clinics were compared with other cardiology OPD for various parameters and it was observed that HF clinics were better than other cardiology OPD in maintaining the medication therapy management.

Clinical Trial Perspective: Cost-effectiveness of Transcatheter Mitral Valve Repair Versus Medical Therapy in Patients with Heart Failure and Secondary Mitral Regurgitation. Results From the COAPT Trial

Treatment of secondary (or functional) mitral regurgitation had traditionally been limited to optimal medical therapy because studies have failed to show a survival benefit with mitral valve surgery for this condition. However, recently the Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation (COAPT) trial demonstrated a significant decrease in heart failure hospitalizations and mortality in patients with severe secondary mitral regurgitation treated with percutaneous edge-to-edge mitral valve repair (TMVr) using the MitraClip device compared with medical therapy. Based o the results of the COAPT trial, the Food and Drug Administration granted approval for MitraClip treatment of patients with severe secondary mitral regurgitation in March 2019. In an attempt to understand the economic impact of treating this patient population with TMVr using the MitraClip device, a formal cost-effectiveness analysis was performed alongside the COAPT trial. This review summarizes the methods and results of the economic substudy of the COAPT trial and discusses the value of the MitraClip device from the perspective of the US healthcare system in the treatment of patients with symptomatic heart failure and secondary mitral regurgitation.

Treatment of Secondary Mitral Regurgitation in Heart Failure: A Shifting Paradigm in the Wake of the COAPT Trial

Secondary mitral regurgitation (MR) is common in patients with left heart dysfunction and it is associated with poor outcomes. Findings from the Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation (COAPT) trial, published in 2018, suggest that in a subset of people with heart failure with secondary MR that persists despite optimization of guideline-directed medical therapies, there is now a role for percutaneous mitral valve repair using the MitraClip device. Defining which patients are most likely to benefit from MitraClip, and when, requires both a multidisciplinary approach centered on heart failure, as well as a recognition of the need for further research in this area.

Functional mitral regurgitation.

Functional mitral regurgitation (FMR) is a complex condition in which significant mitral regurgitation coexist with cardiomyopathy and heart failure and carries an increased risk for associated morbidity and mortality. In addition to guideline-directed medical therapy and cardiac resynchronization therapy, percutaneous transcatheter mitral valve repair (TMVr) is a new therapeutic option but requires careful selection of the proper candidates. We describe the different mechanisms of functional mitral regurgitation, review echocardiographic parameters to assess its severity, and discuss recently published relevant studies including TMVr. Two randomized controlled trials assessing the efficacy and safety of TMVr using the MitraClip in patients with heart failure and severe functional mitral regurgitation were published: MITRA-FR (Percutaneous Repair with the MitraClip Device for Severe Functional/Secondary Mitral Regurgitation) and COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation). The results of these trials were opposite: although MITRA-FR failed to show clinical benefit, COAPT showed a dramatic clinical and echocardiographic benefit from transcatheter mitral valve repair using the MitraClip device. We discuss these two important trials and how differences in patient enrollment could explain the discrepant results and the manner they may influence future studies and clinical practice. Patients with FMR receiving optimal guideline-directed medical therapy and cardiac resynchronization therapy who meet specific clinical and echocardiographic criteria can benefit from transcatheter mitral valve repair.

3-10ANGIOTENSIN RECEPTOR NEPRILYSIN INHIBITORS (ARNI) POTENTIALS IN PATIENT WITH HEART FAILURE: A SYSTEMATIC REVIEW

Background: Structural and/or functional cardiac abnormalities that lead to elevated intracardiac pressures with/without reduced output known as heart failure. Progressive establishment of the disease grows concomitantly with the number of cases despite the availability of various therapies. The recent standard recommends the substitution of angiotensin-converting-enzyme (ACE) inhibitors or angiotensin-II receptor blockers (ARBs) with angiotensin receptor blocker-neprilysin inhibitors (ARNI) in selected patients. The capacity of ARNI will be analyzed based on the latest clinical trials available. Objective: This study focus on revealing the clinical impact and potentials of ARNI in an attempt to counteract the decreasing capacity of the heart. Method: Literature finding involves four scientific databases, including PubMed, EbscoHost, ProQuest, and Cochrane. The primary search was concluded using certain Medical Subject Heading (MeSH) terms and filters. Two independent authors further analyzed selected interventional articles related to ARNI and heart failure. Relevance studies were reviewed using the Centre for Evidence-based Medicine (CEBM) critical appraisal tool to turn aside bias. The result: Data were collected from patients in three randomized controlled trials within five articles. Four of the reports investigate the use of ARNI compared to enalapril in acute decompensated heart failure (ADHF) and chronic heart failure (CHF). Another study compared ARNI to valsartan only therapy in heart failure patients with reduced ejection fraction (HFrEF). It shows that the use of ARNI contributes to a lower number of hospitalization cases and mortality rates while preventing further progression of heart failure. Conclusion: ARNI has adequate potential to prevent the progression of the disease while the encouragement of future investigation is essential.

Heart failure therapy in patients with diabetes

The great interest in the problem “Heart failure” (HF) by the diabetolo­gist has been born in recent years and is mainly linked to the availabil­ity of new antidiabetic drugs which have shown a significant benefit in reducing hospitalizations for heart failure and cardiovascular mortality. Diabetes patients have more than double the risk of developing HF compared to patients without diabetes. The Framingham study has shown that diabetes increases the risk of heart failure up to 2 times in men and 5 times in women compared to controls over age. In addition, 12% of patients with DMT2 have heart failure and 30% of patients with heart failure are diabetic. Hospitalization for HF is associated with very high rates of both post-dis­charge mortality and new hospitalizations. Readmission rates for clinically stable patients discharged after recent hospitalization for HF are approximately 25% at 6 months and all-cause mortality exceeds 30% at 1 year. In particular, a worse prognosis and a longer hospital stay are associated with hospitalized diabetes patients. There is a close correlation between metabolic compensation and HF. In fact, in patients with diabetes a 1% increase in HbA1c is associated with an 8% increase in the risk of HF and still the improvement of the glycometabolic control reduces the risk of HF (in the UKPDS the 1% re­duction in HbA1c was associated with a 16% reduction in the risk of HF occurring). KEY WORDS T2DM; heart failure; SGLT2-inhibitors; diabetic cardiomyopathy.

Heart Failure Patients’ Knowledge and Barriers of Low Sodium Diet Adherence in Erbil City

Background and objective: A low sodium diet is a cornerstone of non-pharmacologic therapy for heart failure patients. The objective of the study was to assess knowledge and perceived barriers of low sodium diet adherence of heart failure patients in Erbil City.Methods: A descriptive, cross-sectional study design was conducted among a sample of 50 patients diagnosed heart failure in Medical Wards and Cardiac Care Units at both Rizgary and Hawler Teaching Hospitals in Erbil City from Feb 2018 to Oct 2019. Patients who met the inclusion criteria were selected for participation of the study, interviews based on a questionnaire patient’s sociodemographic, clinical characteristics and the Dietary Sodium Restriction Questionnaire (DSRQ). Frequency, percentage, and the chi-square test were used for analyzing data.Results: The results show that majority of heart failure patients were low knowledge (80%) and high perceived barriers (66%) to low sodium diet adherence. There were significant associations between knowledge and barrier with age group (p-value=0.01; p-value=0.04), gender, (p-value=0.00; p=0.05), level of education (p-value=0.00; p-value=0.02) and economic status (p-value= < 0.001; p-value= <0.001).Conclusion: Results of the study show that heart failure patients had low knowledge and perceived more barriers to adherence of low sodium diet.

Beta Blocker Therapy in Heart Failure Patients with Active Cocaine Use: A Systematic Review.

Background Cocaine use is associated with multiple cardiovascular complications including heart failure. The use of different types of beta blockers in heart failure patients with active cocaine use is still a matter of debate. In this review, our objective is to systematically review the available literature regarding the use of beta blockers in the treatment of heart failure patients with concurrent cocaine use. Methods PubMed, EMBASE, Web of Science, and Clinical Trials.gov were searched from inception to March 2019 using the Medical Subject Headings (MeSH) terms “cocaine”, “heart failure”, “beta blocker,” and “cardiomyopathy”. Only studies containing the outcomes of heart failure patients with active cocaine use who were treated with beta blockers were included. Results The search resulted in 2072 articles out of which 12 were finally included in the review. A total number of participants were 1994 with a median sample size of 111. Most of the studies were retrospective in nature with Oxford Centre for Evidence-Based Medicine (OCEBM) Levels of Evidence from 3 to 5. The main primary outcomes included readmission rates, mortality, left ventricular ejection fraction (LVEF) improvement, New York Heart Association (NYHA) functional class, and major adverse cardiovascular events (MACEs). In the studies analyzed, beta blockers were found to have either a beneficial or a neutral effect on primary outcomes in heart failure patients with active cocaine use. Conclusion The use of beta blocker therapy appears to be safe and beneficial in heart failure patients with active cocaine use, although the evidence is not robust. Furthermore, large-scale studies are required to confirm this finding.

How to optimize β-blocker therapy in heart failure patients complicating with chronic obstructive pulmonary disease?

心血管疾病和慢性阻塞性肺疾病（COPD）是全球医疗界两大主要健康问题，而共患病则进一步增加了二者的严重程度和病死率。我国心血管病防治工作在取得初步成效的同时，又面临着新的挑战。我国有大量的高血压、冠心病、糖尿病患者，加之人口老龄化问题日益严重，使得我国心力衰竭（心衰）危险人群数量众多。目前，我国心衰患病率估计已达1.3%，至少有1 000万例心衰患者，已经成为全球心衰患者人数最多的国家之一。在心衰患者中，COPD的发病率和患病率较高。吸烟是二者共同的危险因素，同时二者还具有共同的潜在危险因素，如衰老和低度全身性炎症等。但在药物治疗方面，心衰和COPD却存在一定的冲突，如β(2)受体激动剂是COPD患者常用的一种支气管解痉药物，但对心血管系统却有一定的不良影响；另一方面，尽管心衰患者可从β受体阻滞剂治疗中获益，但临床上往往顾虑其对呼吸系统的不良影响而减少了在合并COPD患者中的合理使用。该文就β受体阻滞剂在心衰合并COPD的患者中的应用作一论述。.

Effects of Angiotensin Receptor Neprilysin Inhibition on Vascular Function, Central Pressures and Aortic Wave Reflection Parameters in Heart Failure

Angiotensin Receptor Neprilysin inhibitors (ARNi) are a new therapy for heart failure patients with reduced ejection fraction (HFrEF), which improves vasodilation and diuresis. ARNi is superior to conventional treatment in reducing mortality in HFrEF; this benefit is likely beyond the reduction in both fluid retention and blood pressure (BP). The mechanism(s) for reduced mortality noted with ARNi in HFrEF are unclear but may be related to improved vascular function.PURPOSEWe hypothesized that endothelial function, arterial stiffness, central BP and central wave reflection would improve after 12 weeks of ARNi in HFrEF.METHODSHFrEF participants with New York Heart Association (NYHA) class II‐III were recruited from local cardiology clinics and completed a baseline experimental visit and follow up visit 12 weeks later: 7 patients were prescribed ARNi by their cardiologist [61±11 years, Men: 5, BMI: 31±7 kg/m2, EF: 28±6%; 5 with Non‐ischemic cardiomyopathy (NICM)], and 8 participants continued on conventional treatment [CON: 58±6 years, Men: 5, BMI: 30±5 kg/m2, EF: 30±5% and NICM: 5; all P=NS]. During each experimental visit, endothelial function was assessed by brachial artery flow‐mediated dilation (FMD) using standard techniques. Arterial stiffness was assessed via pulse wave velocity (PWV) (Sphygmocore PVx system). Central aortic BP and surrogate markers of central aortic wave reflection [augmentation index (AIx)] were assessed using radial applanation tonometry; central aortic BP was derived using a generalized transfer function. Statistical comparisons were performed using 2×2 repeated‐measures ANOVA.RESULTSResting mean arterial BP (MAP) was similar between ARNi (94±16 mmHg) and CON (85±10 mmHg; P=0.22); MAP reduced after 12 weeks of ARNi (80±8 mmHg; P=0.01) and was unchanged in CON (89±17 mmHg). At baseline, FMD was similar between ARNi (2.8±3.3%) and CON (5.2±3.6%; P=0.20); however, FMD tended to improve after 12 weeks of ARNi (5.1±1.5%; P=0.07) and remained unchanged in CON (5.4±3.9%). PWV was similar at baseline between ARNi (7.8±2.5 m/s) and CON (7.1±2.8 m/s; P=0.61); PWV reduced after 12 weeks of ARNi (6.5±1.7 m/s; P=0.02) and was unchanged in CON (7.7±2.6 m/s). When PWV was adjusted to MAP, PWV tended to reduce after 12 weeks of ARNi (P=0.07). Aortic systolic BP was similar between ARNi (122±22 mmHg) and CON (108±15 mmHg; P=0.17); aortic systolic BP decreased after 12 weeks of ARNi (106±15 mmHg; P=0.02) but was unchanged in CON (114±26 mmHg). AIx was similar between ARNi (29±15%) and CON (28±14%); and was unchanged after 12 weeks of ARNi (26±8%) and remained unchanged in CON (31±14%; P=NS).CONCLUSIONThese preliminary data suggest that 12 weeks of ARNi therapy reduces blood pressure (peripheral and central) in HFrEF patients. Furthermore, ARNi therapy may improve endothelial function and arterial stiffness. Additional data are needed to fully understand the impact of ARNi on vascular function, aortic BP and aortic wave reflection in HFrEF.Support or Funding InformationACSM grant 19‐00934 and P20 GM 113125

Clinical Effects of CD34+ Cell Therapy in Advanced Chronic Heart Failure Patients Listed for Heart Transplantation

Data on cell therapy in heart failure patients listed for heart transplantation (HTX) are lacking. We sought to investigate the clinical effects of CD34+ cell therapy in this patient cohort. In a single-center retrospective study we analysed data of all patients listed for heart transplantation between 2007 and 2017. Pediatric patients (<18 years), patients with congenital heart disease, mechanical circulatory support, and patients awaiting multi-organ transplantation were excluded. Of 372 patients included, 33 patients (Group A) received CD34+ cell therapy, and 339 (Group B) received optimal medical management. Patients were followed for 1 year; the primary end-point was the rate of delisting from HTX elective waiting list. At the time of HTX listing the two groups did not differ in age (56±7 years in Group A vs. 54±10 years in Group B, P=0.24), gender (male: 100% vs. 80%, P=0.12), heart failure etiology (ishemic; 44% vs. 39%; P=0.55), history of hypertension (61% vs. 59%; P=0.99), renal dysfunction (33% vs. 23%, P=0.46) or diabetes (26% vs 24%, P=0.80). Left ventricular ejection fraction (LVEF: 22±3% vs. 24±4%, P=0.15) and NT-proBNP levels (3524±3821 pg/mL vs. 4048±3482 pg/mL, P=0.64) were also not different between the two groups. Within 1 year after HTX listing patients in both groups did not differ in rates of HTX (48% in Group A vs. 50% in Group B, P=0.88), LVAD implantation (0% in Group A vs. 4% in Group B, P=0.25), or total mortality (3% vs. 10%; p=0.16). However, in Group A, 24% of patients were delisted due to clinical improvement; compared to only 9% of patients in Group B (P=0.005). At the time of HTX listing, the delisted patients displayed similar clinical characteristics than the remaining cohort (LVEF: 22±2% in the delisted vs. 23±4% in the remaining cohort, P=0.67; NT-proBNP: 2822±1198 pg/mL vs. 3983±3927, P=0.45, ishemic heart failure etiology: 43% vs. 39%, P=0.77, history of hypertension: 61% vs. 58%; P=0.82; renal dysfunction: 31% vs. 25%, P=0.44 or diabetes: 20% vs 27%, P=0.52). On multivariate analysis, cell therapy was an independent correlate of delisting (P=0.002). CD 34+ cell therapy appears to be associated with beneficial clinical outcomes and increased rates of delisting in advanced heart failure patients awaiting heart transplantation.

Transcatheter mitral valve repair for functional mitral regurgitation: Evaluating the evidence

ObjectivesTwo trials (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation Trial and Percutaneous Repair with the MitraClip Device for Severe Functional/Secondary Mitral Regurgitation Trial) were published in 2018 evaluating the effectiveness and safety of transcatheter repair for patients with heart failure with significant functional mitral regurgitation, which yielded different results. This article reviews the strength of the evidence, differences in trial designs, ethical and implementation implications, and delineates future research needs to help guide the appropriate dissemination of transcatheter repair for functional patients with mitral regurgitation. MethodsThe National Heart, Lung, and Blood Institute convened a workshop of interdisciplinary experts to address these objectives. ResultsTranscatheter repair of functional mitral regurgitation can provide significant benefits in terms of heart failure hospitalizations, survival, and quality of life when appropriate heart failure candidates with moderate to severe or severe mitral regurgitation while on optimal guideline-directed medical therapy can be identified. Key ingredients for success are preoperative evaluation and management and postoperative care by an interdisciplinary heart team. ConclusionsGiven the discordance observed between trials, ongoing innovation in patient management, and potential expansion of indications for use, the evidence base must be expanded to optimize appropriate implementation of this complex therapy. This will require more complete capture of outcome data in real-world settings for all eligible candidates whether or not they receive this therapy. Inevitably, the indications for use of this therapy will expand, as will the devices and therapeutic approaches for this population, necessitating the study of comparative effectiveness through randomized trials or observational studies. Moreover, given the substantial variations in care delivery, conducting implementation research to delineate characteristics of the optimal care model would be of benefit.

Health Status Changes and Outcomes in Patients With Heart Failure and Mitral Regurgitation: COAPT Trial

BackgroundIn the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) trial, transcatheter mitral valve repair (TMVr) with the MitraClip rapidly improved health status and reduced the long-term risks for death and heart failure (HF) hospitalization in patients with HF and severe secondary mitral regurgitation who remained symptomatic despite maximally tolerated guideline-directed medical therapy (GDMT). ObjectivesThe aim of this study was to examine if early health status changes were associated with long-term clinical outcomes in the COAPT population. MethodsThe association between change in health status (Kansas City Cardiomyopathy Questionnaire overall summary score [KCCQ-OS]) from baseline to 1 month and the composite rate of death or HF hospitalization between 1 month and 2 years in the COAPT trial were evaluated, and whether treatment (TMVr or GDMT alone) modified this association was tested. ResultsAmong 551 patients with HF and severe secondary mitral regurgitation who were alive at 1 month, those randomized to TMVr were more likely than those randomized to GDMT alone to achieve a ≥10-point improvement in KCCQ-OS from baseline to 1 month (TMVr, 58%; GDMT alone, 26%). Early improvement in KCCQ-OS was inversely associated with the risk for death or HF hospitalization between 1 month and 2 years (p < 0.001). When analyzed as a continuous variable, a 10-point increase in KCCQ-OS was associated with a 14% lower risk for death or HF hospitalization (hazard ratio: 0.86; 95% confidence interval: 0.81 to 0.92; p < 0.001), with no significant interaction with treatment group (pinteraction = 0.17). After adjusting for demographic and clinical factors, the association between change in KCCQ-OS and outcomes was strengthened (hazard ratio: 0.79; 95% confidence interval: 0.73 to 0.86; p < 0.001). ConclusionsIn patients with HF and severe secondary mitral regurgitation, a short-term change in disease-specific health status was strongly associated with the subsequent long-term risk for death or HF hospitalization. These findings reinforce the prognostic utility of serial KCCQ-OS assessments to identify patients at risk for poor long-term clinical outcomes in this population. (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation [The COAPT Trial]; NCT01626079)

Real-world experience of leadless left ventricular endocardial cardiac resynchronization therapy: A multicenter international registry of the WiSE-CRT pacing system

BackgroundBiventricular endocardial pacing (BiV ENDO) is a therapy for heart failure patients who cannot receive transvenous epicardial cardiac resynchronization therapy (CRT) or have not responded adequately to CRT. BiV ENDO CRT can be delivered by a new wireless LV ENDO pacing system (WiSE-CRT system; EBR Systems, Sunnyvale, CA), without the requirement for lifelong anticoagulation.ObjectiveThe purpose of this study was to assess the safety and efficacy of the WiSE-CRT system during real-world clinical use in an international registry.MethodsData were prospectively collected from 14 centers implanting the WiSE-CRT system as part of the WiCS-LV Post Market Surveillance Registry. (ClinicalTrials.gov Identifier: NCT02610673).ResultsNinety patients from 14 European centers underwent implantation with the WiSE-CRT system. Patients were predominantly male, age 68.2 ± 10.5 years, left ventricular ejection fraction 30.6% ± 8.9%, mean QRS duration 180.7 ± 27.0 ms, and 40% with ischemic etiology. Successful implantation and delivery of BiV ENDO pacing was achieved in 94.4% of patients. Acute (<24 hours), 1- to 30-day, and 1- to 6-month complications rates were 4.4%, 18.8%, and 6.7%, respectively. Five deaths (5.6%) occurred within 6 months (3 procedure related). Seventy percent of patients had improvement in heart failure symptoms.ConclusionBiV ENDO pacing with the WiSE-CRT system seems to be technically feasible, with a high success rate. Three procedural deaths occurred during the study. Procedural complications mandate adequate operator training and implantation at centers with immediately available cardiothoracic and vascular surgical support.

Short-Term Efficacy and Safety of Tolvaptan in Patients with Left Ventricular Assist Devices.

Tolvaptan is an effective therapy for heart failure patients with symptomatic congestion and hyponatremia. The efficacy of its use in patients with continuous-flow left ventricular assist devices (LVADs) is unknown. The aim of this study was to assess the clinical efficacy and safety of tolvaptan in LVAD patients. We retrospectively reviewed medical records of patients who underwent LVAD implantation between January 2014 and August 2018. Among 217 consecutive LVAD patients, tolvaptan was used in 20 patients. Mean age was 46 ± 14 years old and 14 patients were males. The duration of tolvaptan therapy was 4 (interquartile range 1-8) days. Urine volume significantly increased from 2,623 ± 1,109 ml/day before tolvaptan to 4,308 ± 1,432 ml/day during tolvaptan therapy (p < 0.001). Serum sodium increased from 127 ± 3 to 133 ± 3 mEq/L at the end of tolvaptan therapy (p < 0.001). No patients developed hypernatremia (serum sodium >150 mEq/L). The 90-day overall survival following tolvaptan therapy was 89% in both the tolvaptan group and a propensity score-matched non-tolvaptan group (p = 0.918). Survival free of heart failure readmissions was also comparable between the groups (p = 0.751). In conclusion, short-term use of tolvaptan following LVAD implantation is a safe and effective therapy to augment diuresis and improve hyponatremia.

New Evidence Supporting a Novel Conceptual Framework for Distinguishing Proportionate and Disproportionate Functional Mitral Regurgitation

ImportanceTraditionally, physicians distinguished between mitral regurgitation (MR) as a determinant of outcomes and MR as a biomarker of left-ventricular (LV) dysfunction by designating the lesions as primary or secondary, respectively. In primary MR, leaflet abnormalities cause the MR, resulting in modest increases in LV end-diastolic volume over time, whereas in patients with classic secondary MR, LV dysfunction and dilatation lead to MR without structural leaflet abnormalities. However, certain patients with global LV disease (eg, those with left bundle branch block or regional wall motion abnormalities) have the features of primary MR and might respond favorably to interventions that aim to restore the proper functioning of the mitral valve apparatus.ObservationsA novel conceptual framework is proposed, which classifies patients with meaningful LV disease based on whether the severity of MR is proportionate or disproportionate to the LV end-diastolic volume. Treatments that reduce LV volumes (eg, neurohormonal antagonists) are effective in proportionate MR but not disproportionate MR. Conversely, procedures that restore mitral valve function (eg, cardiac resynchronization and mitral valve repair) are effective in patients with disproportionate MR but not in those with proportionate MR. The proposed framework explains the discordant findings in the Multicentre Randomized Study of Percutaneous Mitral Valve Repair MitraClip Device in Patients With Severe Secondary Mitral Regurgitation (MITRA-FR) and the Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation (COAPT) trials; differences in procedural success and medical therapy in the 2 studies cannot explain the different results. In addition, the small group of patients in the COAPT trial who had the features of proportionate MR and were similar to those enrolled in the MITRA-FR trial did not respond favorably to transcatheter mitral valve repair.Conclusions and RelevanceThe characterization of patients with functional MR into proportionate and disproportionate subtypes may explain the diverse range of responses to drug and device interventions that have been observed.