Selective matrix metalloproteinase inhibition attenuates progression of left ventricular dysfunction and remodeling in dogs with chronic heart failure

2006 ◽  
Vol 290 (6) ◽  
pp. H2522-H2527 ◽  
Author(s):  
Hideaki Morita ◽  
Sanjaya Khanal ◽  
Sharad Rastogi ◽  
George Suzuki ◽  
Makoto Imai ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Interstitial Fibrosis ◽  
Left Ventricular ◽  
High Dose ◽  
Long Term Effects ◽  
Cross Sectional ◽  
Mmp Inhibitor ◽  
Lv Dysfunction

Matrix metalloproteinases (MMPs) contribute to the progression of left ventricular (LV) dysfunction and remodeling associated with heart failure (HF). The present study examined the long-term effects of a selective MMP inhibitor PG-530742 (PG) on the progression of LV dysfunction and remodeling in dogs with HF. Chronic HF [LV ejection fraction (LVEF), ≤36%] was produced by multiple sequential intracoronary microembolizations in 24 dogs. Two weeks after the last embolization, dogs were randomized to 3 mo of therapy with either high-dose (HD) PG (3.5 mg/kg, n = 8), low-dose (LD) PG (0.2 mg/kg, n = 8), or to a matched placebo (PL, n = 8). PG has been shown to produce complete inhibition of MMP-2, -3, -9, and -13, while sparing MMPs-1 and -7. Hemodynamic and echocardiographic measurements were made before and 3 mo after initiating therapy. In PL and LD dogs, LVEF decreased significantly, and LV end-systolic volume (ESV) and LV end-diastolic volume (EDV) increased significantly during the 3-mo follow-up period. Whereas in HD dogs ejection fraction increased from 36 ± 1 to 40 ± 1% ( P = 0.003), EDV and ESV decreased (59 ± 4 vs. 57 ± 4 ml, P = 0.02; and 38 ± 2 vs. 34 ± 2 ml, P = 0.00001, respectively). When compared with controls, HD-treated dogs showed 30% reduction in replacement fibrosis, 29% reduction in interstitial fibrosis, and 28% reduction in myocyte cross-sectional area. mRNA expression of selective MMPs was also reduced in LV tissue in HD- but not LD-treated dogs. In conclusion, in dogs with moderate HF, long-term monotherapy with HD selective MMP inhibitor PG prevents LV remodeling and the progression of global LV dysfunction.

Effects of AT1-receptor blockade on progression of left ventricular dysfunction in dogs with heart failure

1999 ◽  
Vol 276 (4) ◽  
pp. H1385-H1392 ◽  
Author(s):  
Mitsuhiro Tanimura ◽  
Victor G. Sharov ◽  
Hisashi Shimoyama ◽  
Takayuki Mishima ◽  
T. Barry Levine ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Low Dose ◽  
Left Ventricular ◽  
Term Therapy ◽  
High Dose ◽  
Lv Dysfunction ◽  
Lv Ejection Fraction

The objective of the present study was to determine the effects of early long-term monotherapy with the angiotensin II AT1-receptor antagonist valsartan on the progression of left ventricular (LV) dysfunction and remodeling in dogs with moderate heart failure (HF). Studies were performed in 30 dogs with moderate HF produced by multiple sequential intracoronary microembolizations. Embolizations were discontinued when LV ejection fraction was 30–40%. Two weeks after the last embolization, dogs were randomized to 3 mo of oral therapy with low-dose valsartan (400 mg twice daily, n = 10), to high-dose valsartan (800 mg twice daily, n = 10), or to no treatment at all (control, n = 10). Treatment with valsartan significantly reduced mean aortic pressure and LV end-diastolic pressure compared with control. In untreated dogs, LV ejection fraction decreased (37 ± 1 vs. 29 ± 1%, P = 0.001) and end-systolic volume (ESV) and end-diastolic volume (EDV) increased (81 ± 5 vs. 92 ± 5 ml, P < 0.001; 51 ± 3 vs. 65 ± 3 ml, P = 0.001, respectively) after 3 mo of follow-up compared with those levels before follow-up. In dogs treated for 3 mo with low-dose valsartan, ejection fraction was preserved (37 ± 1 vs. 38 ± 2%, pretreatment vs. posttreatment) as was ESV but not EDV. In dogs treated for 3 mo with high-dose valsartan, ejection fraction decreased (35 ± 1 vs. 31 ± 2%, P = 0.02) and ESV and EDV increased in a manner comparable to those levels in controls. Valsartan had no significant effects on cardiomyocyte hypertrophy or on the extent of interstitial fibrosis. We conclude that, for dogs with moderate HF, early long-term therapy with the AT1-receptor blocker valsartan decreases preload and afterload but has only limited benefits in attenuating the progression of LV dysfunction and chamber remodeling.

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 Impact of diabetes mellitus on mortality in patients with acute heart failure: a prospective cohort study

2020 ◽  
Author(s):  
Min Gyu Kong ◽  
Se Yong Jang ◽  
Jieun Jang ◽  
Hyun-Jai Cho ◽  
Sangjun Lee ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Heart Failure ◽  
Glycemic Control ◽  
Ejection Fraction ◽  
Acute Heart Failure ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Inadequate Glycemic Control ◽  
Long Term Mortality

Abstract Background Although more than one third of the patients with acute heart failure (AHF) have diabetes mellitus (DM), it is unclear whether DM exerts adverse impact on clinical outcomes. This study aimed to compare the outcomes in patients hospitalized for AHF in accordance with DM and left ventricular ejection fraction (LVEF). Methods The Korean Acute Heart Failure registry prospectively enrolled and completed follow-up of 5,625 patients from March 2011 to February 2019. Primary endpoints were in-hospital and overall all-cause mortality. We evaluated the impact of DM on these mortalities according to HF subtypes and glycemic control. Results DM was significantly associated with increased long-term mortality (adjusted hazard ratio [HR], 1.12; 95% confidence interval [CI], 1.02-1.22) even after adjusting for potential confounders. In subgroup analysis according to LVEF, DM was associated with higher long-term mortality in only HF with reduced ejection fraction (HFrEF) (adjusted HR, 1.14; 95% CI, 1.02-1.27). Inadequate glycemic control defined by HbA1c ≥ 7.0% within 1 year after discharge was significantly associated with higher long-term mortality compared to adequate glycemic control (HbA1c <7.0%) (44.0% vs. 36.8%; Log-rank p =0.016). Conclusions This large registry data showed that DM and inadequate glycemic control were significantly associated with increased long-term mortality in AHF, especially HFrEF. Tight glucose control is required to mitigate long-term mortality.

scholarly journals Cloud Connected Non-Invasive Medical Device for Instant Left Ventricular Dysfunction Assessment via Any Smartphone (Preprint)

2018 ◽  
Author(s):  
Mark Skowronski ◽  
Kaustubh Kale ◽  
Steven Borzak ◽  
Robert Chait
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Medical Device ◽  
Gold Standard ◽  
Left Ventricular ◽  
Assessment System ◽  
Lv Function ◽  
Time Intervals ◽  
Cardiac Time Intervals ◽  
Lv Dysfunction

BACKGROUND Left Ventricular (LV) dysfunction is the inability of the heart to effectively pump blood through the circulatory system, leading to compensation and eventually heart failure (HF). Ninety-one million American adults with predisposing conditions are at risk for HF and need better screening and diagnosis to prevent disease progression, and 24 million Americans with diagnosed HF need better monitoring to reduce the high hospital readmission rates (25% within 30 days; 50% within 6 months). This epidemic of HF is causing a significant burden on our health care system, with $20 billion in direct medical cost related to HF and $1 billion in in-patient hospital costs annually. Clinical interventions based on standard measurements (blood pressure, weight, electrocardiograms) have not demonstrated a significant reduction in readmissions or all-cause mortality within 180 days after enrollment. Successful treatment may be determined from 2D transthoracic echocardiography (echo) or right heart catherization, but these gold standard methods have limitations of cost, accessibility, and availability of sonographers and cardiologists. An alternative is the HEMOTAG CardioPulmonary Assessment System (CPAS), a new cloud-connected medical device that delivers cardiac time intervals comparable to the gold standard measurements of an echo from an easy-to-use, noninvasive device accessible via any smartphone. OBJECTIVE Given the clinical and economic impact of LV dysfunction and in view of the cost and accessibility of existing devices, there is a need for accurate, absolute, and actionable measurements, available instantly through a noninvasive and easy-to-use system. With the ability of provide rapid assessment of LV dysfunction in adults, keeping patients healthy and safe. The objective of the current study was to compare HEMOTAG to an echo for accuracy in assessment of LV dysfunction, using heart sounds and an ECG signal transduced via 3 thoracic electrodes. METHODS One hundred twenty-three consecutive patients undergoing 2D transthoracic echocardiograms were recruited at an outpatient cardiology clinic from March 2016 through February 2017. Conventional echo variables and cardiac time intervals were assessed, and all patients were analyzed using HEMOTAG which recorded multi-channel acoustic and ECG data. LV dysfunction was assessed using the 2016 American Society of Echocardiography (ASE) standard and compared to cardiac time intervals from HEMOTAG. Patients were separated by age for comparisons. HEMOTAG indices were then assessed to identify normal/abnormal LV function. RESULTS ASE diagnoses: 46 normal, 21 heart failure with preserved ejection fraction (HFpEF), 15 heart failure with reduced ejection fraction (HFrEF), and 41 indeterminate patients. HFrEF was defined as EF <53%, and systolic time ratio (STR=pre-ejection period/ejection time). 0.3 was a sensitive measure for detecting reduced EF as in HFrEF. Detecting EF <53% in patients older than 60: HEMOTAG STR sensitivity=65%, specificity=80%, AUC=.765; Echo STR sensitivity=85%, specificity=80%, AUC=0.895. CONCLUSIONS HEMOTAG represents a potentially widely applicable technology for the assessment of LV dysfunction via a noninvasive approach, providing absolute assessment (without requiring certified technicians to operate or interpretation of an echo) and enabling rapid, real-time, anywhere, anytime assessment of LV dysfunction.

scholarly journals Epidemiology and long-term outcome in outpatients with chronic heart failure in Northwestern Europe

Heart ◽  
2019 ◽  
Vol 105 (16) ◽  
pp. 1252-1259 ◽  
Author(s):  
Hanna Fröhlich ◽  
Niklas Rosenfeld ◽  
Tobias Täger ◽  
Kevin Goode ◽  
Syed Kazmi ◽  
...  
Keyword(s):  
Heart Failure ◽  
Chronic Heart Failure ◽  
Ejection Fraction ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Term Survival ◽  
Period 2 ◽  
Wide Range ◽  
Ambulatory Patients

ObjectiveTo describe the epidemiology, long-term outcomes and temporal trends in mortality in ambulatory patients with chronic heart failure (HF) with reduced (HFrEF), mid-range (HFmrEF) or preserved ejection fraction (HFpEF) from three European countries.MethodsWe identified 10 312 patients from the Norwegian HF Registry and the HF registries of the universities of Heidelberg, Germany, and Hull, UK. Patients were classified according to baseline left ventricular ejection fraction (LVEF) and time of enrolment (period 1: 1995–2005 vs period 2: 2006–2015). Predictors of mortality were analysed by use of univariable and multivariable Cox regression analyses.ResultsAmong 10 312 patients with stable HF, 7080 (68.7%), 2086 (20.2%) and 1146 (11.1%) were classified as having HFrEF, HFmrEF or HFpEF, respectively. A total of 4617 (44.8%) patients were included in period 1, and 5695 (55.2%) patients were included in period 2. Baseline characteristics significantly differed with respect to type of HF and time of enrolment. During a median follow-up of 66 (33–105) months, 5297 patients (51.4%) died. In multivariable analyses, survival was independent of LVEF category (p>0.05), while mortality was lower in period 2 as compared with period 1 (HR 0.81, 95% CI 0.72 to 0.91, p<0.001). Significant predictors of all-cause mortality regardless of HF category were increasing age, New York Heart Association functional class, N-terminal pro-brain natriuretic peptide and use of loop diuretics.ConclusionAmbulatory patients with HF stratified by LVEF represent different phenotypes. However, after adjusting for a wide range of covariates, long-term survival is independent of LVEF category. Outcome significantly improved during the last two decades irrespective from type of HF.

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