Sven Meyer

Acute outcomes of MitraClip therapy for mitral regurgitation in high-surgical-risk patients: emphasis on adverse valve morphology and severe left ventricular dysfunction

AIMSnWe sought to assess the feasibility of catheter-based mitral valve repair using the MitraClip system in high-surgical-risk patients with mitral regurgitation (MR) > or =grade 3+.nnnMETHODS AND RESULTSnMitraClip therapy was performed in 51 consecutive patients [73 +/- 10 years; 34 (67%) men] with symptomatic functional [n = 35 (69%)] or organic MR [n = 16 (31%)]. Mean logistic EuroSCORE was 29 +/- 22%; Society of Thoracic Surgeons score was 15 +/- 11. Left ventricular (LV) ejection fraction was 36 +/- 17%. In 35 patients (69%), adverse mitral valve morphology and/or severe LV dysfunction were present. MitraClip implantation was successful in 49 patients (96%). Most patients [n = 34/49 (69%)] were treated with a single clip, whereas 14 patients (29%) received two clips and one patient received three clips. Mean device and fluoroscopy times were 105 +/- 65 min and 44 +/- 28 min, respectively. Procedure-related reduction in MR severity was one grade in 16 patients (31%), two grades in 24 patients (47%), and three grades in 9 patients (18%). Forty-four of the 49 successfully treated patients (90%) showed clinical improvement at discharge [NYHA functional class > or =III in 48 patients (98%) before and 16 patients (33%) after the procedure (P < 0.0001)]. There were no procedure-related major adverse events and no in-hospital mortality.nnnCONCLUSIONnMitral valve repair using the MitraClip system was shown to be feasible in patients at high surgical risk primarily determined by an adverse mitral valve morphology and/or severe LV dysfunction.

Signature of circulating microRNAs in patients with acute heart failure

Our aim was to identify circulating microRNAs (miRNAs) associated with acute heart failure (AHF).

Neurohormonal and clinical sex differences in heart failure

AIMSnDespite disparities in pathophysiology and disease manifestation between male and female patients with heart failure, studies focusing on sex differences in biomarkers are scarce. The purpose of this study was to assess sex-specific variation in clinical characteristics and biomarker levels to gain more understanding of the potential pathophysiological mechanisms underlying sex differences in heart failure.nnnMETHODS AND RESULTSnBaseline demographic and clinical characteristics, multiple biomarkers, and outcomes were compared between men and women in 567 patients. The mean age of the study group was 71 ± 11 years and 38% were female. Women were older, had a higher body mass index and left ventricular ejection fraction, more hypertension, and received more diuretic and antidepressant therapy, but less ACE-inhibitor therapy compared with men. After 3 years, all-cause mortality was lower in women than men (37.0 vs. 43.9%, multivariable hazard ratio = 0.64; 95% confidence interval 0.45-0.92, P = 0.016). Levels of biomarkers related to inflammation [C-reactive protein, pentraxin 3, growth differentiation factor 15 (GDF-15), and interleukin 6] and extracellular matrix remodelling (syndecan-1 and periostin) were significantly lower in women compared with men. N-terminal pro-brain natriuretic peptide, TNF-αR1a, and GDF-15 showed the strongest interaction between sex and mortality.nnnCONCLUSIONnFemale heart failure patients have a distinct clinical presentation and better outcomes compared with male patients. The lower mortality was independent of differences in clinical characteristics, but differential sex associations between several biomarkers and mortality might partly explain the survival difference.

Sex differences in cardiomyopathies

Cardiomyopathies are a heterogeneous group of heart muscle diseases with a variety of specific phenotypes. According to the contemporary European Society of Cardiology classification, they are classified into hypertrophic (HCM), dilated (DCM), arrhythmogenic right ventricular (ARVC), restrictive (RCM), and unclassified cardiomyopathies. Each class is aetiologically further categorized into inherited (familial) and non‐inherited (non‐familial) forms. There is substantial evidence that biological sex is a strong modulator of the clinical manifestation of these cardiomyopathies, and sex‐specific characteristics are detectable in all classes. For the clinician, it is important to know the sex‐specific aspects of clinical disease expression and the potential modes of inheritance or the hereditary influences underlying the development of cardiomyopathies, since these may aid in diagnosing such diseases in both sexes.

Renal Hemodynamic Effects of Serelaxin in Patients With Chronic Heart Failure: A Randomized, Placebo-Controlled Study

Background—Serelaxin is a promising therapy for acute heart failure. The renal hemodynamic effects of serelaxin in patients with chronic heart failure are unknown. Methods and Results—In this double-blind, randomized, placebo-controlled, multicenter study, patients with New York Heart Association Class II to III chronic heart failure, left ventricular ejection fraction ⩽45%, and estimated glomerular filtration rate (GFR) 30 to 89 mL/min per 1.73 m2 received intravenous serelaxin 30 &mgr;g/kg per day or placebo for 24 hours. Primarily, we assessed the difference between serelaxin and placebo on renal plasma flow (para-aminohippuric acid clearance) and GFR (iothalamate clearance) over 8 to 24 hours. All 22 patients from 1 clinical site were excluded from primary analyses before unblinding because of implausible measurements. The primary analysis comprised 65 patients, mean age was 68 (±10) years, 89% were male, mean estimated GFR was 64 (±19) mL/min per 1.73 m2, and 34% had New York Heart Association Class III symptoms. Renal plasma flow increased by 29% with serelaxin and 14% with placebo (13% relative increase with serelaxin; P=0.0386), whereas GFR changes did not differ significantly during 8 to 24 hours. Filtration fraction increased by 36% with serelaxin and 62% with placebo (16% relative decrease with serelaxin; P=0.0019) during 8 to 24 hours. Changes in systolic blood pressure were largely similar, and creatinine clearance did not differ between groups. Adverse event rates were similar with serelaxin (20.5%) and placebo (25.0%). Conclusions—In patients with chronic heart failure, serelaxin increased renal plasma flow and reduced the increase in filtration fraction compared with placebo, but did not affect GFR. These results suggest beneficial renal hemodynamic effects in patients with chronic heart failure. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT01546532.

Sex-specific acute heart failure phenotypes and outcomes from PROTECT

Differences in manifestation, treatment, and outcomes of acute heart failure between men and women have not been well studied. The objective of this analysis was to characterize differences in clinical presentation, and in‐hospital and post‐discharge outcomes between sexes in acute heart failure patients.

Sex differences in new-onset heart failure.

BackgroundSex differences in patients with established heart failure have been well described, but much less is known in the development of heart failure.MethodsWe studied sex-specific incidence and risk of new-onset heart failure in 8592 subjects (mean age 49.2xa0±xa012.7xa0years; 50.1xa0% women) of the Prevention of REnal and Vascular ENdstage Disease (PREVEND) study and distinguished reduced and preserved ejection fraction (HFrEF <40xa0% and HFpEF >50xa0%).ResultsOf 374 cases with incident heart failure, 241 (64.4xa0%) occurred in men and 133 (35.6xa0%) in women (median follow-up 12.5xa0years; 96,550 person-years). Men developed heart failure earlier (7.0 vs. 8.6xa0years; Pxa0<xa00.001). Incidence rates per 1,000 person-years in women compared to men were lower for HFrEF (1.2 vs. 3.0xa0%; Pxa0<xa00.001), but higher for HFpEF (1.2 vs. 0.7xa0%; Pxa0<xa00.001). Women developed HFpEF later in life than HFrEF (75.1 vs. 69.7xa0years; Pxa0=xa00.033), while men showed no significant difference (72.2 vs. 69.5xa0years; Pxa0=xa00.116). Multivariable competing risks analyses showed that women had lower risk for HFrEF (subhazard ratioxa0=xa00.47; 95xa0% CI 0.29–0.76, Pxa0=xa00.002) but higher risk for HFpEF (subhazard ratioxa0=xa02.16; 95xa0% CI 1.21–3.83, Pxa0=xa00.009) than men. Among all risk factors, only atrial fibrillation had a sex-specific predictive value and increased risk specifically for women (P-for interactionxa0=xa00.016).ConclusionsIn a middle-aged population, men developed heart failure more frequently and at a younger age than women. However, women had higher risk for HFpEF, with atrial fibrillation being a specific female risk factor.

Comparison of instantaneous wave-free ratio (iFR) and fractional flow reserve (FFR) - First real world experience

BACKGROUNDnThe instantaneous wave-free ratio (iFR) is a new adenosine-independent index of coronary stenosis severity. Most published data have been based on off-line analyses of pressure recordings in a core laboratory. We prospectively compared real-time iFR and fractional flow reserve (FFR) measurements.nnnMETHODS AND RESULTSniFR and FFR were measured in 151 coronary stenoses in 108 patients. Repeated iFR measurements were technically simple, showed excellent agreement [rs=0.99; p<0.0001], and the mean difference between consecutive iFR values was 0.0035 (limits of agreement: -0.019, 0.026). Mean iFR showed a significant correlation with FFR [rs=0.81; p<0.0001]. Receiver-operating characteristic analysis identified an optimal iFR cut-off value of 0.896 for categorization based on an FFR cut-off value 0.8. We compared two different iFR-based diagnostic strategies (iFR-only and hybrid iFR-FFR) with standard FFR: The iFR-only strategy showed good classification agreement (83.4%) with standard FFR. Use of the hybrid iFR-FFR strategy, assessing lesions in an iFR-gray zone of 0.86-0.93 by FFR, improved classification accuracy to 94.7%, and diagnosis would have been established in 61% of patients without adenosine-induced hyperemia. Notably, both iFR and FFR values were significantly higher in the posterior coronary vessels.nnnCONCLUSIONSnReal-time iFR measurements are easily performed, have excellent diagnostic performance and confirm available off-line core laboratory data. The excellent agreement between repeated iFR measurements demonstrates the reliability of single measurements. Combining iFR with FFR in a hybrid strategy enhances diagnostic accuracy, exposing fewer patients to adenosine. Overall, iFR is a promising method, but still requires prospective clinical endpoint trial evaluation.

Biomarker Profiles in Heart Failure Patients With Preserved and Reduced Ejection Fraction

Background Biomarkers may help us to unravel differences in the underlying pathophysiology between heart failure (HF) patients with a reduced ejection fraction (HFrEF) and a preserved ejection fraction (HFpEF). Therefore, we compared biomarker profiles to characterize pathophysiological differences between patients with HFrEF and HFpEF. Methods and Results We retrospectively analyzed 33 biomarkers from different pathophysiological domains (inflammation, oxidative stress, remodeling, cardiac stretch, angiogenesis, arteriosclerosis, and renal function) in 460 HF patients (21% HFpEF, left ventricular ejection fraction ≥45%) measured at discharge after hospitalization for acute HF. The association between these markers and the occurrence of all‐cause mortality and/or HF‐related rehospitalizations at 18 months was compared between patients with HFrEF and HFpEF. Patients were 70.6±11.4 years old and 37.4% were female. Patients with HFpEF were older, more often female, and had a higher systolic blood pressure. Levels of high‐sensitive C‐reactive protein were significantly higher in HFpEF, while levels of pro‐atrial‐type natriuretic peptide and N‐terminal pro‐brain natriuretic peptide were higher in HFrEF. Linear regression followed by network analyses revealed prominent inflammation and angiogenesis‐associated interactions in HFpEF and mainly cardiac stretch–associated interactions in HFrEF. The angiogenesis‐specific marker, neuropilin and the remodeling‐specific marker, osteopontin were predictive for all‐cause mortality and/or HF‐related rehospitalizations at 18 months in HFpEF, but not in HFrEF (P for interaction <0.05). Conclusions In HFpEF, inflammation and angiogenesis‐mediated interactions are predominantly observed, while stretch‐mediated interactions are found in HFrEF. The remodeling marker osteopontin and the angiogenesis marker neuropilin predicted outcome in HFpEF, but not in HFrEF.

Sex differences in early dyspnea relief between men and women hospitalized for acute heart failure: insights from the RELAX-AHF study

AimsWomen with heart failure are typically older, and more often have hypertension and a preserved left ventricular ejection fraction as compared with men. We sought to analyze if these sex differences influence the course and outcome of acute heart failure.Methods and resultsWe analyzed sex differences in acute heart failure in 1161 patients enrolled in the RELAX-AHF study. The pre-specified study endpoints were used. At baseline, women (436/1161 patients) were older, had a higher left ventricular ejection fraction, a higher rate of hypertension, and were treated differently from men. Early dyspnea improvement (moderate or marked dyspnea improvement measured by Likert scale during the first 24xa0h) was greater in women. However, dyspnea improvement over the first 5xa0days (change from baseline in the visual analog scale area under the curve (VAS AUC) to day 5) was similar between men and women. Women reported greater improvements in general wellbeing by Likert, but no such benefits were evident with the VAS score. Multi-variable predictors of moderate or marked dyspnea improvement were female sex (pxa0=xa00.0011), lower age (pxa0=xa00.0026) and lower diuretic dose (pxa0=xa00.0067). The additional efficacy endpoints of RELAX-AHF were similar between men and women and serelaxin was equally effective in men and women.ConclusionsWomen exhibit better earlier dyspnea relief and improvement in general wellbeing compared with men, even adjusted for age and left ventricular ejection fraction. However, in-hospital and post-discharge clinical outcomes were similar between men and women.This trial is registered at ClinicalTrials.gov, NCT00520806.