While phosphodiesterase-5 inhibition (PED5i) may prevent hypertrophy and failure in pressure-overloaded heart in an experimental model, the impact of PDE5i on volume-overload (VO)-induced hypertrophy is unknown. It is also unclear whether the hypertrophied right ventricle (RV) and left ventricle (LV) differ in their responsiveness to long-term PDE5i and if this therapy affects renal function. The goal of this study was to elucidate the effect of PDE5i treatment in VO due to aorto-caval fistula (ACF) and to compare PDE5i treatment with standard heart failure (HF) therapy with angiotensin-converting enzyme inhibitor (ACEi). ACF/sham procedure was performed on male HanSD rats aged 8 weeks. ACF animals were randomized for PDE5i sildenafil, ACEi trandolapril, or placebo treatments. After 20 weeks, RV and LV function (echocardiography, pressure-volume analysis), myocardial gene expression, and renal function were studied. Separate rat cohorts served for survival analysis. ACF led to biventricular eccentric hypertrophy (LV: +68%, RV: +145%), increased stroke work (LV: 3.6-fold, RV: 6.7-fold), and reduced load-independent systolic function (PRSW, LV: -54%, RV: -51%). Both ACF ventricles exhibited upregulation of the genes of myocardial stress and glucose metabolism. ACEi but not PDE5i attenuated pulmonary congestion, LV remodeling, albuminuria, and improved survival (median survival in ACF/ACEi was 41 weeks vs. 35 weeks in ACF/placebo, p = .02). PDE5i increased cyclic guanosine monophosphate levels in the lungs, but not in the RV, LV, or kidney. PDE5i did not improve survival rate and cardiac and renal function in ACF rats, in contrast to ACEi. VO-induced HF is not responsive to PDE5i therapy.

• Klíčová slova
• heart failure, phosphodiesterase-5 inhibition, rats, right ventricle, volume overload,
• MeSH
• inhibitory ACE * farmakologie   MeSH
• inhibitory fosfodiesterasy 5 * farmakologie   MeSH
• kardiomegalie farmakoterapie   MeSH
• krysa rodu Rattus MeSH
• remodelace komor * MeSH
• srdeční selhání * farmakoterapie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• inhibitory ACE * MeSH
• inhibitory fosfodiesterasy 5 * MeSH

BACKGROUND: Heart failure is a common complication after myocardial infarction (MI) and is associated with increased mortality. Whether remote heart failure symptoms assessment after MI can improve risk stratification is unknown. The authors evaluated the association of the 23-item Kansas City Cardiomyopathy Questionnaire (KCCQ) with all-cause mortality after MI. METHODS AND RESULTS: Prospectively collected data from consecutive patients hospitalized for MI at a large tertiary heart center between June 2017 and September 2022 were used. Patients remotely completed the KCCQ 1 month after discharge. A total of 1135 (aged 64±12 years, 26.7% women) of 1721 eligible patients completed the KCCQ. Ranges of KCCQ scores revealed that 30 (2.6%), 114 (10.0%), 274 (24.1%), and 717 (63.2%) had scores <25, 25 to 49, 50 to 74, and ≥75, respectively. During a mean follow-up of 46 months (interquartile range, 29-61), 146 (12.9%) died. In a fully adjusted analysis, KCCQ scores <50 were independently associated with mortality (hazard ratio [HR], 6.05 for KCCQ <25, HR, 2.66 for KCCQ 25-49 versus KCCQ ≥50; both P<0.001). Adding the 30-day KCCQ to clinical risk factors improved risk stratification: change in area under the curve of 2.6 (95% CI, 0.3-5.0), Brier score of -0.6 (95% CI, -1.0 to -0.2), and net reclassification improvement of 0.71 (95% CI, 0.45-1.04). KCCQ items most strongly associated with mortality were walking impairment, leg swelling, and change in symptoms. CONCLUSIONS: Remote evaluation of heart failure symptoms using the KCCQ among patients recently discharged for MI identifies patients at risk for mortality. Whether closer follow-up and targeted therapy can reduce mortality in high-risk patients warrants further study.

• Klíčová slova
• KCCQ, heart failure, mortality, myocardial infarction, prognosis, symptoms,
• MeSH
• hospitalizace MeSH
• infarkt myokardu * komplikace   diagnóza   MeSH
• kvalita života MeSH
• lidé MeSH
• proporcionální rizikové modely MeSH
• propuštění pacienta MeSH
• srdeční selhání * terapie   MeSH
• zdravotní stav MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Background The hypocretin/orexin system has been shown to play a role in heart failure. Whether it also influences myocardial infarction (MI) outcomes is unknown. We evaluated the effect of the rs7767652 minor allele T associated with decreased transcription of the hypocretin/orexin receptor-2 and circulating orexin A concentrations on mortality risk after MI. Methods and Results Data from a single-center, prospectively designed registry of consecutive patients hospitalized for MI at a large tertiary cardiology center were analyzed. Patients without previous history of MI or heart failure were included. A random population sample was used to compare allele frequencies in the general population. Out of 1009 patients (aged 64±12 years, 74.6% men) after MI, 6.1% were homozygotes (TT) and 39.4% heterozygotes (CT) for minor allele. Allele frequencies in the MI group did not differ from 1953 subjects from general population (χ2 P=0.62). At index hospitalization, MI size was the same, but ventricular fibrillation and the need for cardiopulmonary resuscitation were more prevalent in the TT allele variant. Among patients with ejection fraction ≤40% at discharge, the TT variant was associated with a lower increase in left ventricular ejection fraction during follow-up (P=0.03). During the 27-month follow-up, there was a statistically significant association of the TT variant with increased mortality risk (hazard ratio [HR], 2.83; P=0.001). Higher circulating orexin A was associated with a lower mortality risk (HR, 0.41; P<0.05). Conclusions Attenuation of hypocretin/orexin signaling is associated with increased mortality risk after MI. This effect may be partially explained by the increased arrhythmic risk and the effect on the left ventricular systolic function recovery.

• Klíčová slova
• hypocretin/orexin receptor‐2, hypocretin/orexin system, inflammation, mortality, myocardial infarction, outcomes, recovery,
• MeSH
• funkce levé komory srdeční MeSH
• infarkt myokardu * MeSH
• lidé MeSH
• orexinové receptory genetika   MeSH
• orexiny genetika   MeSH
• srdeční selhání * MeSH
• tepový objem MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• orexinové receptory MeSH
• orexiny MeSH

AIMS: Identification of heart failure (HF) patients with secondary mitral regurgitation (SMR) that benefit from mitral valve (MV) repair remains challenging. We have focused on the role of left ventricular global longitudinal strain (LV-GLS) and reservoir left atrial longitudinal strain (LASr) for the prediction of long-term survival and reverse remodelling in patients with SMR undergoing endoscopic MV repair. METHODS AND RESULTS: The study population consisted of 110 patients (age 67 ± 11 years, 66% men) with symptomatic SMR undergoing isolated MV repair using a minimally invasive surgical approach. Speckle tracking-derived LV-GLS and LASr were assessed in apical views using vendor-independent software. Over a median of 7.7 years (IQRs 2.9-11.2), 64 patients (58%) died. Significant reverse LV (↓ LVESVI >10 mL/m2 ), LA (↓ LAVI >10 mL/m2 ) remodelling or both were observed in 43 (39%), 37 (34%) and 19 (17%) patients, respectively. LV-GLS (HR 0.68, 95% CI 0.58-0.79, P < 0.001) and LASr (HR 0.93, 95% CI 0.88-0.97, P < 0.01) but not LV ejection fraction (LVEF) and LA volume index (LAVi) emerged as independent predictors of all-cause mortality in Cox regression analysis. LV-GLS was the only independent predictor of LV reverse remodelling (OR 1.24, 95% CI 1.05-1.43, P < 0.001) whereas LAVi and LASr were both independent predictors of LA reverse remodelling (both P < 0.05). In patients with atrial fibrillation at baseline, only LASr was an independent predictor (P < 0.05) of LA reverse remodelling. CONCLUSIONS: In patients with SMR undergoing endoscopic MV repair, LV-GLS and LASr are independently associated with long-term survival and reverse remodelling and may be helpful in selecting SMR patients who may benefit from this procedure.

• Klíčová slova
• Endoscopic mitral valve repair, Reverse remodelling, Secondary mitral regurgitation, Strain, Survival,
• MeSH
• funkce levé komory srdeční MeSH
• kardiochirurgické výkony * MeSH
• lidé středního věku MeSH
• lidé MeSH
• mitrální chlopeň diagnostické zobrazování   chirurgie   MeSH
• mitrální insuficience * diagnóza   chirurgie   MeSH
• senioři MeSH
• tepový objem MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH