An anti-angiogenic cleaved prolactin fragment is considered causal for peripartum cardiomyopathy (PPCM). Experimental and first clinical observations suggested beneficial effects of the prolactin ...release inhibitor bromocriptine in PPCM.
In this multicentre trial, 63 PPCM patients with left ventricular ejection fraction (LVEF) ≤35% were randomly assigned to short-term (1W: bromocriptine, 2.5 mg, 7 days) or long-term bromocriptine treatment (8W: 5 mg for 2 weeks followed by 2.5 mg for 6 weeks) in addition to standard heart failure therapy. Primary end point was LVEF change (delta) from baseline to 6 months assessed by magnetic resonance imaging. Bromocriptine was well tolerated. Left ventricular ejection fraction increased from 28 ± 10% to 49 ± 12% with a delta-LVEF of + 21 ± 11% in the 1W-group, and from 27 ± 10% to 51 ± 10% with a delta-LVEF of + 24 ± 11% in the 8W-group (delta-LVEF: P = 0.381). Full-recovery (LVEF ≥ 50%) was present in 52% of the 1W- and in 68% of the 8W-group with no differences in secondary end points between both groups (hospitalizations for heart failure: 1W: 9.7% vs. 8W: 6.5%, P = 0.651). The risk within the 8W-group to fail full-recovery after 6 months tended to be lower. No patient in the study needed heart transplantation, LV assist device or died.
Bromocriptine treatment was associated with high rate of full LV-recovery and low morbidity and mortality in PPCM patients compared with other PPCM cohorts not treated with bromocriptine. No significant differences were observed between 1W and 8W treatment suggesting that 1-week addition of bromocriptine to standard heart failure treatment is already beneficial with a trend for better full-recovery in the 8W group.
ClinicalTrials.gov, study number: NCT00998556.
In-hospital cardiac arrest (IHCA) is associated with poor outcomes. There are currently no standards for cardiac arrest teams in terms of member composition and task allocation. Here we aimed to ...compare two different cardiac arrest team concepts to cover IHCA management in terms of survival and neurological outcomes. This prospective study enrolled 412 patients with IHCA from general medical wards. From May 2014 to April 2016, 228 patients were directly transferred to the intensive care unit (ICU) for ongoing resuscitation. In the ICU, resuscitation was extended to advanced cardiac life support (ACLS) (Load-and-Go LaG group). By May 2016, a dedicated cardiac arrest team provided by the ICU provided ACLS in the ward. After return of spontaneous circulation (ROSC), the patients (n = 184) were transferred to the ICU (Stay-and-Treat SaT group). Overall, baseline characteristics, aetiologies, and characteristics of cardiac arrest were similar between groups. The time to endotracheal intubation was longer in the LaG group than in the SaT group (6 5, 8 min versus 4 2, 5 min, p = 0.001). In the LaG group, 96% of the patients were transferred to the ICU regardless of ROSC achievement. In the SaT group, 83% of patients were transferred to the ICU (p = 0.001). Survival to discharge did not differ between the LaG (33%) and the SaT (35%) groups (p = 0.758). Ultimately, 22% of patients in the LaG group versus 21% in the SaT group were discharged with good neurological outcomes (p = 0.857). In conclusion, we demonstrated that the cardiac arrest team concepts for the management of IHCA did not differ in terms of survival and neurological outcomes. However, a dedicated (intensive care) cardiac arrest team could take some load off the ICU.
Sex- and flow-related aortic valve calcification (AVC) studies are still limited in number, and data on the exact calcium quantity and distribution are scarce. Therefore, we aimed to (1) re-define ...the best threshold of AVC load to distinguish severe from moderate aortic stenosis (AS) in common AS entities and to (2) evaluate differences in the aortic annulus and left ventricular outflow tract (LVOT) calcium load. Nine hundred and thirty-eight patients with contrast-enhanced cardiac MSCT and moderate-to-severe aortic stenosis (AS) were retrospectively enrolled. Patients with severe AS ≤ 1.0 cm
2
(
n
= 841) were further separated into three AS entities: high gradient (HGAS,
n
= 370, 44.0%), paradoxical low gradient (pLGAS,
n
= 333, 39.6%), and classical low gradient (LGAS,
n
= 138, 16.4%). AVC, leaflet, and LVOT calcification were quantified. Aortic valve calcification scores were highest in severe HGAS, and lower in severe pLGAS and classical LGAS. In all severity and AS entities, the non-coronary cusp (NCC) was the most calcified one. LVOT calcification was consistently comparable between gender and AS entities. Accuracy of logistic regression was the highest in HGAS (male vs. female: AVC > 2156 Agatston units (AU), c-index 0.76; vs. AVC > 1292 AU, c-index 0.85; or AVC density > 406 AU/cm
2
, c-index 0.82; vs. > 259 AU/cm
2
, c-index 0.86; each
p
< 0.0001*) to diagnose severe AS. AVC could only be used in men to differentiate between severe LGAS and moderate AS. Data from this retrospective analysis indicate that the NCC is subject to pre-dominant degeneration throughout gender, AS severity, and several AS entities. AVC was consistently comparable in severe pLGAS and classical LGAS, but only AVC in severe LGAS could sufficiently distinguish from moderate AS in men. LVOT calcification failed to be a reliable indicator of accelerating AS.
We aimed to identify predictors of mitral regurgitation recurrence (MR) after percutaneous mitral valve repair (PMVR) in patients with functional mitral regurgitation (FMR). Patients with FMR were ...enrolled who underwent PMVR using the MitraClip
®
device. Procedural success was defined as reduction of MR of at least one grade to MR grade ≤ 2 + assessed at discharge. Recurrence of MR was defined as MR grade 3 + or worse at one year after initially successful PMVR. A total of 306 patients with FMR underwent PMVR procedure. In 279 out of 306 patients (91.2%), PMVR was successfully performed with MR grade ≤ 2 + at discharge. In 11.4% of these patients, MR recurrence of initial successful PMVR after 1 year was observed. Recurrence of MR was associated with a higher rate of heart failure rehospitalization during the 12 months follow-up (52.0% vs. 30.3%;
p
= 0.029), and less improvement in New York Heart Association (NYHA) functional class 68% vs. 19% of the patients presenting with NYHA functional class III or IV one year after PMVR when compared to patients without recurrence (
p
= 0.001). Patients with MR recurrence were characterized by a higher left ventricular sphericity index {0.69 Interquartile range (IQR) 0.64, 0.74 vs. 0.65 (IQR 0.58, 0.70),
p
= 0.003}, a larger left atrium volume 118 (IQR 96, 143) ml vs. 102 (IQR 84, 123) ml,
p
= 0.019, a larger tenting height 10 (IQR 9, 13) mm vs. 8 (IQR 7, 11) mm (
p
= 0.047), and a larger mitral valve annulus 41 (IQR 38, 43) mm vs. 39 (IQR 36, 40) mm,
p
= 0.015 when compared to patients with durable optimal long-term results. In a multivariate regression model, the left ventricular sphericity index Odds Ratio (OR) 1.120, 95% Confidence Interval (CI) 1.039–1.413,
p
= 0.003), tenting height (OR 1.207, 95% CI 1.031–1.413,
p
= 0.019), and left atrium enlargement (OR 1.018, 95% CI 1.000–1.038,
p
= 0.047) were predictors for MR recurrence after 1 year. In patients with FMR, baseline parameters of advanced heart failure such as spherical ventricle, tenting height and a large left atrium might indicate risk of recurrent MR one year after PMVR.
The hemodynamic vascular consequences of implanting left ventricular assist devices (LVADs) have not been studied in detail. We investigated the effect of LVAD implantation compared with heart ...transplant (HTx) on microvascular and macrovascular function in patients with end-stage heart failure and evaluated whether microparticles may play a role in LVAD-related endothelial dysfunction.
Vascular function was assessed in patients with end-stage heart failure awaiting HTx, patients who had undergone implantation of a continuous-flow centrifugal LVAD, and patients who had already received a HTx. Macrovascular function was measured by flow-mediated vasodilation (FMD) using high-resolution ultrasound of the brachial artery. Microvascular function was assessed in the forearm during reactive hyperemia using laser Doppler perfusion imaging and pulsed wave Doppler. Age-matched patients without heart failure and without coronary artery disease (CAD) (healthy control subjects) and patients with stable CAD served as control subjects. Circulating red blood cell (CD253(+)), leukocyte (CD45(+)), platelet (CD31(+)/CD41(+)), and endothelial cell (CD31(+)/CD41(-), CD62e(+), CD144(+)) microparticles were determined by flow cytometry and free hemoglobin by enzyme-linked immunosorbent assay.
FMD and microvascular function were significantly impaired in patients with end-stage heart failure compared with healthy control subjects and patients with stable CAD. LVAD implantation led to recovery of microvascular function, but not FMD. In parallel, increased free hemoglobin was observed along with red and white cell microparticles and endothelial and platelet microparticles. This finding indicates destruction of blood cells with release of hemoglobin and activation of endothelial cells. HTx and LVAD implantation led to similar improvements in microvascular function. FMD increased and microparticle levels decreased in patients with HTx, whereas shear stress during reactive hyperemia was similar in patients with LVADs and patients with HTx.
Our data suggest that LVAD support leads to significant improvements in microvascular perfusion and hemodynamics. However, destruction of blood cells may contribute to residual endothelial dysfunction potentially by increasing nitric oxide scavenging capacity.
While most patients recover from suspected acute myocarditis (sAMC) some develop progressive disease with 5-year mortality up to 20%. Recently, parametric Cardiovascular Magnetic Resonance (CMR) ...approaches, quantifying native T1 and T2 relaxation time, have demonstrated the ability to increase diagnostic accuracy. However, prognostic implications of T2 values in this cohort are unknown. The purpose of the study was to investigate the prognostic relevance of elevated CMR T2 values in patients with sAMC.
We carried out a prospective study in 46 patients with sAMC defined by current ESC recommendations. A combined endpoint was defined by the occurrence of at least one major adverse cardiac event (MACE) and hospitalisation for heart failure. Event rate was 24% (n = 11) for 1-year-MACE and hospitalisation. A follow-up after 11 ± 7 months was performed in 98% of the patients. Global T2 values were significantly increased at acute stage of disease compared to controls and decreased over time. During acute disease, elevated global T2 time (odds ratio 6.3, p < 0.02) as well as myocardial fraction with T2 time >80 ms (odds ratio 4.9, p < 0.04) predicted occurrence of the combined endpoint. Patients with clinical recovery revealed significantly decreased T2 relaxation times at follow-up examinations; however, T2 values were still elevated compared to healthy controls.
Assessment of myocardial T2 relaxation times at initial presentation facilitates CMR-based risk stratification in patients with acute myocarditis. T2 Mapping may emerge as a new tool to monitor inflammatory myocardial injuries during the course of disease.
OBJECTIVESThe aim of this study was to develop a machine learning (ML)-based risk stratification tool for 1-year mortality in transcatheter mitral valve repair (TMVR) patients incorporating metabolic ...and hemodynamic parameters. BACKGROUNDThe lack of appropriate, well-validated, and specific means to risk-stratify patients with mitral regurgitation complicates the evaluation of prognostic benefits of TMVR in clinical trials and practice. METHODSA total of 1,009 TMVR patients from 3 university hospitals within the Heart Failure Network Rhineland were included; 1 hospital (n = 317) served as external validation. The primary endpoint was all-cause 1-year mortality. Model performance was assessed using receiver-operating characteristic curve analysis. In the derivation cohort, different ML algorithms were tested using 5-fold cross-validation. The final model, called MITRALITY (transcatheter mitral valve repair mortality prediction system) was tested in the validation cohort with respect to existing clinical scores. RESULTSExtreme gradient boosting was selected for the MITRALITY score, using only 6 baseline clinical features for prediction (in order of predictive importance): urea, hemoglobin, N-terminal pro-brain natriuretic peptide, mean arterial pressure, body mass index, and creatinine. In the external validation cohort, the MITRALITY score's area under the curve was 0.783 (95% CI: 0.716-0.849), while existing scores yielded areas under the curve of 0.721 (95% CI: 0.63-0.811) and 0.657 (95% CI: 0.536-0.778) at best. CONCLUSIONSThe MITRALITY score is a novel, internally and externally validated ML-based tool for risk stratification of patients prior to TMVR, potentially serving future clinical trials and daily clinical practice.
Recurrent mitral regurgitation (MR) following MitraClip has not been thoroughly investigated. We aimed to examine the predictive factors, morphology, and long-term outcome of recurrent MR after ...MitraClip.
We assessed data from the Heart Failure Network Rhineland registry from August 2010 to October 2018. Competing risk analyses were performed using the Fine and Gray model to assess the risk of recurrent MR.
Among 685 MitraClip patients with a reduction in MR to ≤2+, 61 patients developed recurrent MR within the first 12 months. Flail leaflet (hazard ratio, 3.68;
=0.002) and residual MR (MR grade 2+ versus ≤1+: hazard ratio, 2.56;
=0.03) were the predictors of recurrent MR in primary MR patients, while left atrial volume (per 10 mL increase: hazard ratio, 1.11;
<0.001) and residual MR (hazard ratio, 2.45;
=0.01) were independently associated with recurrent MR in secondary MR patients. In primary MR patients, loss of leaflet insertion or leaflet tear were the predominant morphologies with recurrent MR. In secondary MR patients, more than half of the patients with recurrent MR did not show any disorder of the clip or leaflets. Patients with recurrent MR were more likely to experience unplanned heart failure hospitalization or heart failure symptom with New York Heart Association scale III/IV (54.1% versus 37.8%;
=0.018) and undergo a repeat mitral valve intervention (9.8% versus 2.2%;
=0.005) during the follow-up. In the landmark survival analysis, patients with recurrent MR tended to have lower long-term survival (58.7% versus 83.9%;
=0.08) than patients without recurrent MR.
Flail leaflet and residual MR were the predictors of recurrent MR in primary MR patients, while a larger left atrial volume and residual MR were associated with recurrent MR in secondary MR patients, which may be associated with long-term clinical outcomes of patients after MitraClip.
We investigated aortic valve calcification (AVC) distribution and predictors for leaflet calcification patterns in patients with severe tricuspid aortic valve stenosis undergoing transcatheter aortic ...valve replacement (TAVR). Patients undergoing routine multi-sliced computed tomography (MSCT) for procedural planning were enrolled. MSCT data were transferred to a dedicated workstation for evaluation (3mensio Structural Heart™, Pie Medical Imaging BV, Maastricht, The Netherlands) and analyzed. Participants were separated into asymmetrical (AC) and symmetrical (SC) leaflet calcification and potential predictors for calcification distribution were identified with univariate and multivariate regression analysis. 567 Participants with severe tricuspid AS were divided into asymmetrical (AC, n = 443; 78.1%) and symmetrical (SC, n = 124; 21.9%) AVC. In AC, the non-coronary cusp was the most calcified cusp (n = 238; 57.7%). SC is more common in females (AC/SC: 49.2% vs. 67.7%; p < 0.0001). AVC was more severe in patients with AC, who also have larger aortic root dimensions. Multivariate analysis depicted, inter alia, left ventricular outflow tract (LVOT) calcification < 25 Agatston units (OR 1.81 1.09–3.00, p = 0.021), a mean pressure gradient < 36 mmHg (OR 1.77 1.03–3.05, p = 0.039), and an annulo-apical angle > 67° (OR 1.68 1.00–2.80, p = 0.049) as predictors for SC, although with only moderate predictive value. Data from this retrospective analysis indicate that SC occurs more frequently in females. The cumulative leaflet calcification burden is higher in patients with AC, who also present with larger aortic root dimensions. The predictive value for prominent calcification of different aortic valve cusps in AC patients was only low to moderate.
Trial registration number
: NCT01805739.
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