scholarly journals Cpxm2 as a novel candidate for cardiac hypertrophy and failure in hypertension

2021 ◽  
Author(s):  
Katja Grabowski ◽  
Laura Herlan ◽  
Anika Witten ◽  
Fatimunnisa Qadri ◽  
Andreas Eisenreich ◽  
...  
Keyword(s):  
Ejection Fraction ◽  
Cardiac Hypertrophy ◽  
Transcriptome Analysis ◽  
Genetic Locus ◽  
Left Ventricular ◽  
Cardiac Damage ◽  
Rat Cardiomyocytes ◽  
Spontaneously Hypertensive ◽  
Reduced Ejection Fraction ◽  
Systolic And Diastolic Function

AbstractTreatment of hypertension-mediated cardiac damage with left ventricular (LV) hypertrophy (LVH) and heart failure remains challenging. To identify novel targets, we performed comparative transcriptome analysis between genetic models derived from stroke-prone spontaneously hypertensive rats (SHRSP). Here, we identified carboxypeptidase X 2 (Cpxm2) as a genetic locus affecting LV mass. Analysis of isolated rat cardiomyocytes and cardiofibroblasts indicated Cpxm2 expression and intrinsic upregulation in genetic hypertension. Immunostaining indicated that CPXM2 associates with the t-tubule network of cardiomyocytes. The functional role of Cpxm2 was further investigated in Cpxm2-deficient (KO) and wild-type (WT) mice exposed to deoxycorticosterone acetate (DOCA). WT and KO animals developed severe and similar systolic hypertension in response to DOCA. WT mice developed severe LV damage, including increases in LV masses and diameters, impairment of LV systolic and diastolic function and reduced ejection fraction. These changes were significantly ameliorated or even normalized (i.e., ejection fraction) in KO-DOCA animals. LV transcriptome analysis showed a molecular cardiac hypertrophy/remodeling signature in WT but not KO mice with significant upregulation of 1234 transcripts, including Cpxm2, in response to DOCA. Analysis of endomyocardial biopsies from patients with cardiac hypertrophy indicated significant upregulation of CPXM2 expression. These data support further translational investigation of CPXM2.

P2470The prognostic importance and inter-relationship of systolic and diastolic tissue Doppler velocities in heart failure patients with reduced ejection fraction

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M Sengelov ◽  
P G Jorgensen ◽  
N E Bruun ◽  
T Fritz-Hansen ◽  
F J Olsen ◽  
...  
Keyword(s):  
Ejection Fraction ◽  
Diastolic Function ◽  
Tissue Doppler ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
P Value ◽  
Ventricular Ejection Fraction ◽  
Reduced Ejection Fraction ◽  
Systolic And Diastolic Function ◽  
Relationship Of

Abstract Background Tissue Doppler imaging (TDI) can be used to evaluate both the systolic and diastolic function in patients with heart failure with reduced ejection fraction (HFrEF). However, previous studies have shown important inter-relationship between these measures in other patient populations. Purpose To investigate the prognostic importance and inter-relationship of systolic and diastolic TDI measures in HFrEF. Methods Conventional echocardiographic measurements together with peak longitudinal systolic (s'), early diastolic (e'), and late diastolic (a') myocardial velocities from all 6 myocardial walls were obtained from 1065 HFrEF patients. Outcome was all-cause mortality. Results Mean age was 67 years, 74% were male and mean left ventricular ejection fraction was 27%. During a median follow-up period of 40 months, 177 (16.6%) patients died. In univariable analyses, both s' and a' were associated with mortality (p<0.001), but e' was not (p>0.05). Patients were therefore stratified into high/low groups by the mean value of s' and a' respectively. The prognostic value of s' was significantly modified by a' (p for interaction 0.035). In patients with low s', low a' was associated with an increased risk of dying; HR 1.31 (CI: 1.17–1.55, P=0.001) per 1 cm/s decrease. Patients with both impaired systolic and diastolic function as assessed by low s' and a' had over 3 times greater risk of dying compared to having both high measures of s' and a' (HR 3.39, CI: 2.1–5.1, p<0.001) (figure). Having combined impaired systolic and diastolic function as assessed by low s' and a' remained an independent predictor of mortality even after multivariable adjustment for age, gender, body mass index, mean arterial pressure, ischemic cardiomyopathy, pacemaker, heart rate, total cholesterol, diabetes and conventional echocardiographic measures (HR 1.78 (CI: 1.04–3.04, p=0.035) (table)). Uni- and multivariable Cox regressions Variable Univariable model (95% CI) Multivariable model* HR (95% CI) P value HR (95% CI) P value High s' and high a' (n=386) Ref Ref High s' and low a' (n=113) 1.48 (1.07–4.03) 0.24 1.36 (0.69–2.70) 0.37 Low s' and high a' (n=156) 2.26 (1.34–3.81) 0.002 1.55 (0.86–2.78) 0.14 Low s' and low a' (n=262) 3.29 (2.43–5.75) <0.001 1.78 (1.04–3.04) 0.035 *Multivariable model adjusted for age, gender, body mass index, mean arterial pressure, ischemic cardiomyopathy, pacemaker, heart rate, total cholesterol, diabetes, left ventricular ejection fraction, left ventricular mass index, and deceleration time. Kaplan-Meier curves depicting survival Conclusion A pattern of combined low systolic and diastolic performance as assessed by s' and a' is a significant marker of adverse prognosis for patients with HFrEF, independent of conventional echocardiographic parameters. Acknowledgement/Funding None

Heart Failure with Preserved Ejection Fraction – A Review

2012 ◽  
Vol 9 (1) ◽  
pp. 90-95 ◽  
Author(s):  
Otto A Smiseth ◽  
Anders Opdahl ◽  
Espen Boe ◽  
Helge Skulstad
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Diastolic Heart Failure ◽  
The Elderly ◽  
Left Ventricular ◽  
Filling Pressure ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Reduced Ejection Fraction ◽  
Objective Evidence

Heart failure with preserved left ventricular ejection fraction (HF-PEF), sometimes named diastolic heart failure, is a common condition most frequently seen in the elderly and is associated with arterial hypertension and left ventricular (LV) hypertrophy. Symptoms are attributed to a stiff left ventricle with compensatory elevation of filling pressure and reduced ability to increase stroke volume by the Frank-Starling mechanism. LV interaction with stiff arteries aggravates these problems. Prognosis is almost as severe as for heart failure with reduced ejection fraction (HF-REF), in part reflecting co-morbidities. Before the diagnosis of HF-PEF is made, non-cardiac etiologies must be excluded. Due to the non-specific nature of heart failure symptoms, it is essential to search for objective evidence of diastolic dysfunction which, in the absence of invasive data, is done by echocardiography and demonstration of signs of elevated LV filling pressure, impaired LV relaxation, or increased LV diastolic stiffness. Antihypertensive treatment can effectively prevent HF-PEF. Treatment of HF-PEF is symptomatic, with similar drugs as in HF-REF.

Prognostic value of global longitudinal layer specific strain for patients with heart failure with reduced ejection fraction

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
C Johnsen ◽  
M Sengeloev ◽  
P Joergensen ◽  
N Bruun ◽  
D Modin ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Prognostic Value ◽  
Left Ventricular ◽  
Volume Index ◽  
Funding Source ◽  
Reduced Ejection Fraction ◽  
Patients With Heart Failure ◽  
All Cause Mortality ◽  
Echocardiographic Parameters

Abstract Background Novel echocardiographic software allows for layer-specific evaluation of myocardial deformation by 2-dimensional speckle tracking echocardiography. Endocardial, epicardial- and whole wall global longitudinal strain (GLS) may be superior to conventional echocardiographic parameters in predicting all-cause mortality in patients with heart failure with reduced ejection fraction (HFrEF). Purpose The purpose of this study was to investigate the prognostic value of endocardial-, epicardial- and whole wall GLS in patients with HFrEF in relation to all-cause mortality. Methods We included and analyzed transthoracic echocardiographic examinations from 1,015 patients with HFrEF. The echocardiographic images were analyzed, and conventional and novel echocardiographic parameters were obtained. A p value in a 2-sided test &lt;0.05 was considered statistically significant. Cox proportional hazards regression models were constructed, and both univariable and multivariable hazard ratios (HRs) were calculated. Results During a median follow-up time of 40 months, 171 patients (16.8%) died. A lower endocardial (HR 1.17; 95% CI (1.11–1.23), per 1% decrease, p&lt;0.001), epicardial (HR 1.20; 95% CI (1.13–1.27), per 1% decrease, p&lt;0.001), and whole wall (HR 1.20; 95% CI (1.14–1.27), per 1% decrease, p&lt;0.001) GLS were all associated with higher risk of death (Figure 1). Both endocardial (HR 1.12; 95% CI (1.01–1.23), p=0.027), epicardial (HR 1.13; 95% CI (1.01–1.26), p=0.040) and whole wall (HR 1.13; 95% CI (1.01–1.27), p=0.030) GLS remained independent predictors of mortality in the multivariable models after adjusting for significant clinical parameters (age, sex, total cholesterol, mean arterial pressure, heart rate, ischemic cardiomyopathy, percutaneous transluminal coronary angioplasty and diabetes) and conventional echocardiographic parameters (left ventricular (LV) ejection fraction, LV mass index, left atrial volume index, deceleration time, E/e', E-velocity, E/A ratio and tricuspid annular plane systolic excursion). No other echocardiographic parameters remained an independent predictors after adjusting. Furthermore, endocardial, epicardial and whole wall GLS had the highest C-statistics of all the echocardiographic parameters. Conclusion Endocardial, epicardial and whole wall GLS are independent predictors of all-cause mortality in patients with HFrEF. Furthermore, endocardial, epicardial and whole wall GLS were superior prognosticators of all-cause mortality compared with all other echocardiographic parameters. Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): Herlev and Gentofte Hospital

Effect of Sacubitril/Valsartan Combined with Dapagliflozin on Long-Term Cardiac Mortality in Heart Failure with Reduced Ejection Fraction

Angiology ◽  
2021 ◽  
pp. 000331972110473
Author(s):  
Umut Karabulut ◽  
Kudret Keskin ◽  
Dilay Karabulut ◽  
Ece Yiğit ◽  
Zerrin Yiğit
Keyword(s):  
Heart Failure ◽  
Combination Therapy ◽  
Ejection Fraction ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Cardiac Mortality ◽  
Ventricular Ejection Fraction ◽  
Reduced Ejection Fraction ◽  
Neprilysin Inhibitor

The angiotensin receptor–neprilysin inhibitor (ARNI) sacubitril/valsartan and sodium-glucose cotransporter-2 (SGLT-2) inhibitor dapagliflozin have been shown to reduce rehospitalization and cardiac mortality in patients with heart failure (HF) with reduced ejection fraction (HFrEF). We aimed to compare the long-term cardiac and all-cause mortality of ARNI and dapagliflozin combination therapy against ARNI monotherapy in patients with HFrEF. This retrospective study involved 244 patients with HF with New York Heart Association (NYHA) class II–IV symptoms and ejection fraction ≤40%. The patients were divided into 2 groups: ARNI monotherapy and ARNI+dapagliflozin. Median follow-up was 2.5 (.16–3.72) years. One hundred and seventy-five (71.7%) patients were male, and the mean age was 65.9 (SD, 10.2) years. Long-term cardiac mortality rates were significantly lower in the ARNI+dapagliflozin group (7.4%) than in the ARNI monotherapy group (19.5%) ( P = .01). Dapagliflozin [Hazard Ratio (HR) [95% Confidence Interval (CI)] = .29 [.10–.77]; P = .014] and left ventricular ejection fraction (LVEF) [HR (95% CI) = .89 (.85–.93); P < .001] were found to be independent predictors of cardiac mortality. Our study showed a significant reduction in cardiac mortality with ARNI and dapagliflozin combination therapy compared with ARNI monotherapy.

scholarly journals Long-term outcomes in patients with critical limb ischemia and heart failure with preserved or reduced ejection fraction

2017 ◽  
Vol 22 (4) ◽  
pp. 307-315 ◽  
Author(s):  
Kavita B Khaira ◽  
Ellen Brinza ◽  
Gagan D Singh ◽  
Ezra A Amsterdam ◽  
Stephen W Waldo ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Critical Limb Ischemia ◽  
Limb Ischemia ◽  
Left Ventricular ◽  
Term Survival ◽  
Long Term Survival ◽  
Reduced Ejection Fraction ◽  
History Of

The impact of heart failure (HF) on long-term survival in patients with critical limb ischemia (CLI) has not been well described. Outcomes stratified by left ventricular ejection fraction (EF) are also unknown. A single center retrospective chart review was performed for patients who underwent treatment for CLI from 2006 to 2013. Baseline demographics, procedural data and outcomes were analyzed. HF diagnosis was based on appropriate signs and symptoms as well as results of non-invasive testing. Among 381 CLI patients, 120 (31%) had a history of HF and 261 (69%) had no history of heart failure (no-HF). Within the HF group, 74 (62%) had HF with preserved ejection fraction (HFpEF) and 46 (38%) had HF with reduced ejection fraction (HFrEF). The average EF for those with no-HF, HFpEF and HFrEF were 59±13% vs 56±9% vs 30±9%, respectively. The likelihood of having concomitant coronary artery disease (CAD) was lowest in the no-HF group (43%), higher in the HFpEF group (70%) and highest in the HFrEF group (83%) ( p=0.001). Five-year survival was on average twofold higher in the no-HF group (43%) compared to both the HFpEF (19%, p=0.001) and HFrEF groups (24%, p=0.001). Long-term survival rates did not differ between the two HF groups ( p=0.50). There was no difference in 5-year freedom from major amputation or freedom from major adverse limb events between the no-HF, HFpEF and HFrEF groups, respectively. Overall, the combination of CLI and HF is associated with poor 5-year survival, independent of the degree of left ventricular systolic dysfunction.

scholarly journals Long-Term clinical outcomes of subcutaneous implantable defibrillator therapy in patients with heart failure and reduced ejection fraction: a single center experience

EP Europace ◽  
2021 ◽  
Vol 23 (Supplement_3) ◽  
Author(s):  
M Ben Kilani ◽  
P Jacon ◽  
A Carabelli ◽  
S Venier ◽  
P Defaye
Keyword(s):  
Ejection Fraction ◽  
Real Life ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Reduced Ejection Fraction ◽  
Cardioverter Defibrillator ◽  
Patients With Heart Failure ◽  
The Mean

Abstract Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): P. JACON consultant: Boston Scientific France Introduction The implantable cardioverter defibrillator (ICD) is the most effective therapy for prevention of sudden cardiac death in high-risk patients with heart failure and reduced ejection fraction (HFrEF). The subcutaneous implantable cardioverter defibrillator (S-ICD) has been considered as a comparable and relatively safer alternative to transvenous ICD in patients (pts) without pacing indication. Purpose Our aim was to assess the clinical "real-life" outcomes of S-ICD in patients with HFrEF and primary or secondary prevention, over a long-term follow-up (FU) period after S-ICD implantation. Methods All pts with HFrEF (left ventricular ejection fraction ≤35%) implanted with a S-ICD and a FU above 6 months were included in a cross-sectional monocentric study. Pts were followed by remote monitoring. Results 88 pts were included (52 ± 12.8 years old, male 87.5%). Indications were: primary 92% and secondary 8% prevention  (ischemic cardiopathy 46%; dilated 46%; hypertrophic 5%; congenital 2%; valvular 1%). The mean left ventricular ejection fraction was 27%. 9 pts had a previous transvenous ICD implanted, but required revision because of infection or lead defects. The mean FU period was 33 ± 18 months with a mortality rate of 10% (S-ICD-related death secondary to inappropriate (inap) shocks for one patient). 5 pts underwent S-ICD system extraction after a mean FU period of 30 ± 21 months. Reasons were infectious complication (1 pt), pacing indication (2 pts) and S-ICD lead dysfunction (2 pts). Extraction after heart transplant was performed in 4 pts. During FU, 18 pts (20.5%) experienced at least one therapy: 8 pts (9%) with appropriate (ap) (3.3% per year) and 11 pts (12%) with inap shocks (4.36% per year). A total number of 24 ap shocks have been observed (3 ± 4 ap shocks per patient, several shocks for 3 pts), the first shock occurred after a mean FU period of 24 ± 14 months. 2 pts were referred to VT ablation and no recurrence of events was observed after medical therapy modification for the other pts. For the 11 pts with inap shocks, time to the first event was 19 ± 20 months. Reasons were: supraventricular arrhythmias (18%), T wave (36%) and noise (54%) oversensing. There was 1.8 ± 1.6 shock per patient with several shocks for 4 pts. Among pts with inap shocks, 2 pts required S-ICD system extraction, 1 pt died, while reprogramming and medical therapy options were efficient in other pts. Conclusion In pts with HFrEF at high risk of sudden cardiac death, S-ICD has proven to be effective in treating ventricular arrhythmias. However, more investigations must be conducted to explain the real-life high rate of inappropriate therapies. Abstract Figure. Survival-free from therapies curve

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