@article{AlbertLeziusStoerketal.2021,
  author    = {Albert, Judith and Lezius, Susanne and St{\"o}rk, Stefan and Morbach, Caroline and G{\"u}der, G{\"u}lmisal and Frantz, Stefan and Wegscheider, Karl and Ertl, Georg and Angermann, Christiane E.},
  title     = {Trajectories of Left Ventricular Ejection Fraction After Acute Decompensation for Systolic Heart Failure: Concomitant Echocardiographic and Systemic Changes, Predictors, and Impact on Clinical Outcomes},
  series = {Journal of the American Heart Association},
  volume    = {10},
  journal   = {Journal of the American Heart Association},
  doi       = {10.1161/JAHA.120.017822},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-230210},
  year      = {2021},
  abstract  = {Prospective longitudinal follow-up of left ventricular ejection fraction (LVEF) trajectories after acute cardiac decompensation of heart failure is lacking. We investigated changes in LVEF and covariates at 6-months' follow-up in patients with a predischarge LVEF ≤40\%, and determined predictors and prognostic implications of LVEF changes through 18-months' follow-up. Methods and Results Interdisciplinary Network Heart Failure program participants (n=633) were categorized into subgroups based on LVEF at 6-months' follow-up: normalized LVEF (>50\%; heart failure with normalized ejection fraction, n=147); midrange LVEF (41\%-50\%; heart failure with midrange ejection fraction, n=195), or persistently reduced LVEF (≤40\%; heart failure with persistently reduced LVEF , n=291). All received guideline-directed medical therapies. At 6-months' follow-up, compared with patients with heart failure with persistently reduced LVEF, heart failure with normalized LVEF or heart failure with midrange LVEF subgroups showed greater reductions in LV end-diastolic/end-systolic diameters (both P<0.001), and left atrial systolic diameter (P=0.002), more increased septal/posterior end-diastolic wall-thickness (both P<0.001), and significantly greater improvement in diastolic function, biomarkers, symptoms, and health status. Heart failure duration <1 year, female sex, higher predischarge blood pressure, and baseline LVEF were independent predictors of LVEF improvement. Mortality and event-free survival rates were lower in patients with heart failure with normalized LVEF (P=0.002). Overall, LVEF increased further at 18-months' follow-up (P<0.001), while LV end-diastolic diameter decreased (P=0.048). However, LVEF worsened (P=0.002) and LV end-diastolic diameter increased (P=0.047) in patients with heart failure with normalized LVEF hospitalized between 6-months' follow-up and 18-months' follow-up. Conclusions Six-month survivors of acute cardiac decompensation for systolic heart failure showed variable LVEF trajectories, with >50\% showing improvements by ≥1 LVEF category. LVEF changes correlated with various parameters, suggesting multilevel reverse remodeling, were predictable from several baseline characteristics, and were associated with clinical outcomes at 18-months' follow-up. Repeat hospitalizations were associated with attenuation of reverse remodeling."},
  language  = {en}
}
@article{FrantzKlaiberBabaetal.2013,
  author    = {Frantz, Stefan and Klaiber, Michael and Baba, Hideo A. and Oberwinkler, Heinz and V{\"o}lker, Katharina and Gaßner, Birgit and Bayer, Barbara and Abeßer, Marco and Schuh, Kai and Feil, Robert and Hofmann, Franz and Kuhn, Michaela},
  title     = {Stress-dependent dilated cardiomyopathy in mice with cardiomyocyte-restricted inactivation of cyclic GMP-dependent protein kinase I},
  series = {European Heart Journal},
  volume    = {34},
  journal   = {European Heart Journal},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-134693},
  pages     = {1233-1244},
  year      = {2013},
  abstract  = {Aims: Cardiac hypertrophy is a common and often lethal complication of arterial hypertension. Elevation of myocyte cyclic GMP levels by local actions of endogenous atrial natriuretic peptide (ANP) and C-type natriuretic peptide (CNP) or by pharmacological inhibition of phosphodiesterase-5 was shown to counter-regulate pathological hypertrophy. It was suggested that cGMP-dependent protein kinase I (cGKI) mediates this protective effect, although the role in vivo is under debate. Here, we investigated whether cGKI modulates myocyte growth and/or function in the intact organism. Methods and results: To circumvent the systemic phenotype associated with germline ablation of cGKI, we inactivated the murine cGKI gene selectively in cardiomyocytes by Cre/loxP-mediated recombination. Mice with cardiomyocyte-restricted cGKI deletion exhibited unaltered cardiac morphology and function under resting conditions. Also, cardiac hypertrophic and contractile responses to β-adrenoreceptor stimulation by isoprenaline (at 40 mg/kg/day during 1 week) were unaltered. However, angiotensin II (Ang II, at 1000 ng/kg/min for 2 weeks) or transverse aortic constriction (for 3 weeks) provoked dilated cardiomyopathy with marked deterioration of cardiac function. This was accompanied by diminished expression of the \([Ca^{2+}]_i\)-regulating proteins SERCA2a and phospholamban (PLB) and a reduction in PLB phosphorylation at Ser16, the specific target site for cGKI, resulting in altered myocyte \(Ca^{2+}_i\) homeostasis. In isolated adult myocytes, CNP, but not ANP, stimulated PLB phosphorylation, \(Ca^{2+}_i\)-handling, and contractility via cGKI. Conclusion: These results indicate that the loss of cGKI in cardiac myocytes compromises the hypertrophic program to pathological stimulation, rendering the heart more susceptible to dysfunction. In particular, cGKI mediates stimulatory effects of CNP on myocyte \(Ca^{2+}_i\) handling and contractility.},
  language  = {en}
}