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Archive for the ‘Heart Failure (HF)’ Category


Changes in Levels of Sex Hormones and N-Terminal Pro–B-Type Natriuretic Peptide as Biomarker for Cardiovascular Diseases

Reporter and Curator: Dr. Sudipta Saha, Ph.D.

 

Considerable differences exist in the prevalence and manifestation of atherosclerotic cardiovascular disease (CVD) and heart failure (HF) between men and women. Premenopausal women have a lower risk of CVD and HF compared with men; however, this risk increases after menopause. Sex hormones, particularly androgens, are associated with CVD risk factors and events and have been postulated to mediate the observed sex differences in CVD.

 

B-type natriuretic peptides (BNPs) are secreted from cardiomyocytes in response to myocardial wall stress. BNP plays an important role in cardiovascular remodelling and volume homeostasis. It exerts numerous cardioprotective effects by promoting vasodilation, natriuresis, and ventricular relaxation and by antagonizing fibrosis and the effects of the renin-angiotensin-aldosterone system. Although the physiological role of BNP is cardioprotective, pathologically elevated N-terminal pro–BNP (NT-proBNP) levels are used clinically to indicate left ventricular hypertrophy, dysfunction, and myocardial ischemia. Higher NT-proBNP levels among individuals free of clinical CVD are associated with an increased risk of incident CVD, HF, and cardiovascular mortality.

 

BNP and NT-proBNP levels are higher in women than men in the general population. Several studies have proposed the use of sex- and age-specific reference ranges for BNP and NT-proBNP levels, in which reference limits are higher for women and older individuals. The etiology behind this sex difference has not been fully elucidated, but prior studies have demonstrated an association between sex hormones and NT-proBNP levels. Recent studies measuring endogenous sex hormones have suggested that androgens may play a larger role in BNP regulation by inhibiting its production.

 

Data were collected from a large, multiethnic community-based cohort of individuals free of CVD and HF at baseline to analyze both the cross-sectional and longitudinal associations between sex hormones [total testosterone (T), bioavailable T, freeT, dehydroepiandrosterone (DHEA), SHBG, and estradiol] and NT-proBNP, separately for women and men. It was found that a more androgenic pattern of sex hormones was independently associated with lower NT-proBNP levels in cross-sectional analyses in men and postmenopausal women.

 

This association may help explain sex differences in the distribution of NT-proBNP and may contribute to the NP deficiency in men relative to women. In longitudinal analyses, a more androgenic pattern of sex hormones was associated with a greater increase in NT-proBNP levels in both sexes, with a more robust association among women. This relationship may reflect a mechanism for the increased risk of CVD and HF seen in women after menopause.

 

Additional research is needed to further explore whether longitudinal changes in NT-proBNP levels seen in our study are correlated with longitudinal changes in sex hormones. The impact of menopause on changes in NT-proBNP levels over time should also be explored. Furthermore, future studies should aim to determine whether sex hormones directly play a role in biological pathways of BNP synthesis and clearance in a causal fashion. Lastly, the dual role of NTproBNP as both

  • a cardioprotective hormone and
  • a biomarker of CVD and HF, as well as
  • the role of sex hormones in delineating these processes,

should be further explored. This would provide a step toward improved clinical CVD risk stratification and prognostication based on

  • sex hormone and
  • NT-proBNP levels.

 

References:

 

https://www.medpagetoday.com/clinical-connection/cardio-endo/76480?xid=NL_CardioEndoConnection_2018-12-27

 

https://www.ncbi.nlm.nih.gov/pubmed/30137406

 

https://www.ncbi.nlm.nih.gov/pubmed/22064958

 

https://www.ncbi.nlm.nih.gov/pubmed/24036936

 

https://www.ncbi.nlm.nih.gov/pubmed/19854731

 

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Paraoxonase 2 (PON2) appears to play a cardioprotective role in both human and experimental heart failure: Cardiologist Wai Hong Wilson Tang, MD, Director of Cleveland Clinic Lerner Research Institute’s Center for Clinical Genomics.

Reporter: Aviva Lev-Ari, PhD, RN

Enzyme Protects Heart Against Stress and Could Potentially Lead to New Heart Failure Treatments

https://consultqd.clevelandclinic.org/enzyme-protects-heart-against-stress-and-could-potentially-lead-to-new-heart-failure-treatments/amp/?__twitter_impression=true

Original Study:
 2018 Jun;121:117-126. doi: 10.1016/j.freeradbiomed.2018.04.583. Epub 2018 May 2.

Paraoxonase 2 prevents the development of heart failure.

Abstract

BACKGROUND:

Mitochondrial oxidation is a major source of reactive oxygen species (ROS) and mitochondrial dysfunction plays a central role in development of heart failure (HF). Paraoxonase 2 deficient (PON2-def) mitochondria are impaired in function. In this study, we tested whether PON2-def aggravates HF progression.

METHODS AND RESULTS:

Using qPCR, immunoblotting and lactonase activity assay, we demonstrate that PON2 activity was significantly decreased in failing hearts despite increased PON2 expression. To determine the cardiac-specific function of PON2, we performed heart transplantations in which PON2-def and wild type (WT) donor hearts were implanted into WT recipient mice. Beating scores of the donor hearts, assessed at 4 weeks post-transplantation, were significantly decreased in PON2-def hearts when compared to WT donor hearts. By using a transverse aortic constriction (TAC) model, we found PON2 deficiency significantly exacerbated left ventricular remodeling and cardiac fibrosis post-TAC. We further demonstrated PON2 deficiency significantly enhanced ROS generation in heart tissues post-TAC. ROS generation was measured through dihydroethidium (DHE) using high-pressure liquid chromatography (HPLC) with a fluorescent detector. By using neonatal cardiomyocytes treated with CoCl2 to mimic hypoxia, we found PON2 deficiency dramatically increased ROS generation in the cardiomyocytes upon CoCl2 treatment. In response to a short CoCl2 exposure, cell viability and succinate dehydrogenase (SDH) activity assessed by MTT assay were significantly diminished in PON2-def cardiomyocytes compared to those in WT cardiomyocytes. PON2-def cardiomyocytes also had lower baseline SDH activity. By using adult mouse cardiomyocytes and mitochondrial ToxGlo assay, we found impaired cellular ATP generation in PON2-def cells compared to that in WT cells, suggesting that PON2 is necessary for proper mitochondrial function.

CONCLUSION:

Our study suggests a cardioprotective role for PON2 in both experimental and human heart failure, which may be associated with the ability of PON2 to improve mitochondrial function and diminish ROS generation.

KEYWORDS:

Cardiomyopathy; Heart failure; Paraoxonase 2

PMID:
29729330
PMCID:
PMC5971153
 [Available on 2019-06-01]
DOI:
10.1016/j.freeradbiomed.2018.04.583

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NHLBI decision to halt Heart Stem-Cell Study (CONCERT-HF trial) due to concerns about Anversa’s Animal Studies, not due to any Data generated by the Clinical trial itself, no compromised patient safety by trial

Reporter: Aviva Lev-Ari, PhD, RN

Doubts about Anversa’s work arose in the early 2000s after other researchers failed to replicate his findings and questioned whether cardiac stem cells existed2,3,4.

Paper of Former HMS Prof. Withdrawn, Clinical Trial Paused after Harvard Requests Retractions

https://www.thecrimson.com/article/2018/10/31/medical-school-paper-retracted/

NHLBI NEWS

Statement

Statement on NHLBI decision to pause the CONCERT-HF trial

The National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health, is pausing the CONCERT-HF trialexternal link, which involves patients with chronic heart failure. Recent calls for the retraction of journal articles in related fields of cell therapy research have raised concerns about the scientific foundations of this trial.  While none of the articles in question derive from the CONCERT-HF trial itself, the NHLBI convened CONCERT-HF’s Data and Safety Monitoring Board (DSMB) out of an abundance of caution to ensure the study continues to meet the highest standards for participant safety and scientific integrity. Informed by the DSMB recommendations of October 25, 2018, the NHLBI is pausing the trial. While the DSMB did not have any participant safety concerns, this pause enables the DSMB to complete its review.

The safety of all clinical trial participants is paramount to NHLBI. NHLBI will honor its commitment to CONCERT-HF participants and continue the follow-up protocol during this pause for all participants who have already been treated in the study. Participants are being notified of the status of the trial and how to request additional information.

The CONCERT-HF trial seeks to determine whether c-kit+ cells, either alone or in combination with mesenchymal stem cells derived from the bone marrow, are safe and benefit patients with chronic heart failure, who have very limited treatment options. Despite significant medical and surgical advances, patients with heart failure continue to experience a low quality of life and about half of them will die within five years of receiving a diagnosis.

The scientific basis of CONCERT-HF is supported by a body of evidence in several preclinical models in a number of studies in a variety of laboratories and was reviewed by a Protocol Review Committee (PRC) independent of the trial. The cell therapies that CONCERT-HF is testing are under an investigational new drug (IND) designation which is overseen by the U.S. Food and Drug Administration (FDA). The cells are produced by an accredited laboratory independent of the clinical sites. In addition, as part of standard oversight of clinical trials, the DSMB routinely reviews and monitors CONCERT-HF to ensure participant safety and that the study continues to ask compelling scientific questions with implications for patient care.

The DSMB’s review will be conducted as expeditiously as possible and will inform NHLBI’s future actions that will ensure the highest standards of participant safety and scientific integrity.

SOURCE

https://www.nhlbi.nih.gov/news/2018/statement-nhlbi-decision-pause-concert-hf-trial

References

  1. Quaini, F. et al. N. Engl. J. Med. 346, 5–15 (2002).
  1. Murry, C. E. et al. Nature 428, 664–668 (2004).
  1. Balsam, L. B. Nature 428, 668–673 (2004).
  1. Nygren, J. M. et al. Nature Med. 10, 494–501 (2004).

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Live 2:30-4:30 PM  Mediterranean Diet and Lifestyle: A Symposium on Diet and Human Health:  October 19, 2018

Reporter: Stephen J. Williams, Ph.D.

 

2:30 Mediterranean Diet, Intangible Heritage and Sustainable Tourism?

Prof. Fabio Parasecoli, PhD.

 

 

Nutrition and Food Department, New York University

We focus on more of the cultural aspects and the relevance of this diet to tourism in Italy where there is a high rate of unemployment.  The diet is interesting from a touristic standpoint as the diet have the perspective of the different ingredients inherent in Italy.  The mediterranean diet food pyramid totally different than US.  How do we explain to consumers these medical concepts; for example in China, Germany they are using different ways to explain the benefits of this diet.

A Cultural Formation

  • a way of life, for tourism there is the way of life people want to adopt (easiest way to do this is go to the Mediterranean and learn the lifestyle)
  • so for example Olive Garden for marketing purposes sent a few chefs for half a day training so the image of learning to cook in the mediterranean diet style can be very powerful communicative tool
  • 2003 UNESCO Convention for Safeguarding the Culturing Heritage: protecting landscapes but then decided to protect other intangible heritage like oral, language, oral traditions like transmitting recipes, social and festive events (how do we cook how do we grow tomatoes, wheat etc)
  • UNESCO: promoted France Gastronomic, Mediterranean Diet, and traditional Mexican Cuisine (Mayan)
  • defined Greece, Italy, Morroco then included Cyprus Crotia and Portugal in the Mediterranean diet
  • has it been used for promotion: no UNESCO did not use this since does not safeguard the culture
  • (gastrodiplomacy); like Korea and kimchie; included in the list of cultural cuisine but can create tourist bubbles as you tourism places like hotels don’t always use; for reasons of economy or safety or accessibility , local food
  • Centrality of Territorio:  food consumed from tourist should come from the area

Sustainable Tourism: a form of tourism where have the intention to get to know the place;

have to think in three ways

  1. environmental
  2. social
  3. cultural

how do we make a circular economy so no waste; for example certain companies using food waste to make other products

Tourism clusters made of many groups; he is working on a way to jump start these networks in Nigeria;

Sustainable Food Supply Chain Tourism can be used as way to engage people and promote the diet

Question: are there regions where people are not adopting the diet because of taste, preferences

Yes there is always a problem with accessibility, affordability, trade issues and regional acceptance. For instance in Australia a big push back against the Mediterranean diet.  Medical professionals need to work with communication experts and media experts in developing ways to communicate the benefits since “no one wants to be preached at” and “as economies get richer people want to be more modern and try new things”

In Nigeria we are working with many different industries like transportation, engineers, the IT industry and chefs to build a scalable model

 

3.00 Italy as a Case Study: Increasing Students’ Level of Awareness of the Historical, Cultural, Political and Culinary Significance of Food

Prof. Lisa Sasson

Nutrition and Food Department, New York University

Started a program at NYU to understand food  from a nutritionist and historical point of view as a cultural heritage in Italy, but when students came back students mentioned it changed their food shopping habits

they described diet as wine, pasta, and olive oil

Artisional Production:  understanding the taste and flavor; she wanted them to learn about the food culture and educate their tastes

Food Memories: how we pass on recipes and food aromas, food tastes.  The students were experienced food in a unique way for the first time, experiencing what cheese, quality oil other foods when fresh tastes like.  Artisional foods may be expensive but need only a little of it because the tastes and flavors are so potent due to the phytochemicals

Within six months students:

  1. increased consumption of weekly wine consumption with meals
  2. increased consuming satisfying meals
  3. increased time consuming meals

In the womb the fetus is actually acquiring sense of taste (amniotic fluid changes with mother diet; can detect flavor chemicals)

Student Perceptions after a study Abroad Program

  • eating foods local and seasonal
  • replacing butter with quality olive oil
  • using herbs
  • very little sugar
  • unsweetened beverages
  • limiting red meats
  • fish a couple of times a week
  • dairy in moderation
  • no processed foods

Eating and Dining for Americans is a Challenge:  The students ate well and satisfying meals but ate alot but did not gain weight

3:30 Italian Migration and Global Diaspora

Dr. Vincenzo Milione, PhD

Director of Demographics Studies, Calandra Institute, City University of New York

for a PDF of this presentation please click heresbarro handout.

Dr. Millione used the U.S. Census Bureau Data to estimate the growth of the Italian diaspora descendants in host countries in the Americas and to determine the mixed global ancestry of Italian descendants.

  • Italian emigration to the US happened in two waves
  1.            Wave 1: early 1900 peaking between 1901 and 1911 (turn of century)
  2.            Wave 2: 1951-1971 (post WWII)

This pattern was similar between North and South America although South American had first Italian immigration; in 1860 we got rid of slavery so many jobs not filled new orleans

Developing a mathematical model of Italian diaspora: the model is centered on the host country population dynamics but descendants are separated into first generation and multi generation

Model dependent on:

  • birth and death rates
  • first generation population growth
  • multi generational population growth
  • emigration from host country over time

He was able to calculate an indices he termed Year of Italianization Change (YIC): the year the growth of the multi generation supercedes the first generation immigrant population 

Country Year of Italianlization Change (YIC)
Brazil 1911
Uruguay 1915
Argentina 1918
USA 1936
Venezuela 1963
Canada 1968
Australia 1988

 

note: as a result there is an increasing loss of language and traditional customs with host country cultural adaptation among the native born descendants

In addition, over the last 20 years Italian-American population growth demonstrates that Italian-American self-identity in the United States has increased.  The census data identified two ancestries of the respondent.  In mixed ancestry Italian-American respondents to the extent they identify Italian first demonstrating the strong Italian-American identity.

The foreign born Italian Americans mirror the immigration pattern of Italian immigration from Italy until 1980 where more Italian Americans self identify as foreign born in other countries and not in Italy

Summary

  • over 5 million Italians have emigrated from Italy from 1980 to present
  • most went to North and South America but many went to other global countries
  • the Italian immigration to the different countries in the Americas varies over the period of mass emigration when the growth of multi generational Italian descendants is greater then first generation Italians (Year of Italianization Change) goes from 1911 in Brazil to 1988 in Australia
  • Immigrants to the USA was not just from Italy but from almost all nations globally over all geographical continents
  • Italina immigrants descendants greatly grew after 1930 with appreciable increase with other ethnicities such that 61% of Italian Americans are mixed ancestry in 2014: to date mixed ancestry represents 98% of Italian Americans
  • younger italian americans more likely to have mixed ancestry with Central and South America, Asian and African ethnicities

over time during immigration eating habits has changed but more research is needed if and how the italian recipes and diet has changed as well

 

4:15 Conclusions

Prof. Antonio Giordano, MD, PhD.

To follow or Tweet on Twitter please use the following handles (@) and hashtags (#):

@ handles


@S_H_R_O 

@SbarroHealth

@Pharma_BI 

@ItalyinPhilly

@WHO_Europe

@nutritionorg

# hashtags


#healthydiet

#MediterraneanDiet

#health

#nutrition

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Two Classes of Antithrombotic Drugs: Anticoagulants and Antiplatelet drugs

Reporter: Aviva Lev-Ari, PhD, RN
These drugs are used to treat
  • strokes,
  • myocardial infarctions,
  • pulmonary embolisms,
  • disseminated intravascular coagulation (DIC) and
  • deep vein thrombosis (DVT)
— all potentially life-threatening conditions.
THERAPEUTIC STRATEGIES
• Degrade fibrinogen/fibrin (fibrinolytic agents)
GOAL: eliminate formed clots
• Inhibit clotting mechanism (anticoagulants)
GOAL: prevent progression of thrombosis
• Interfere either with platelet adhesion and/or aggregation (antiplatelet drugs)
GOAL: prevent initial clot formation
Antithrombotic therapy has had an enormous impact in several significant ways.
  • Heparin has made bypass surgery and dialysis possible by blocking clotting in external tubing.
  • Antithrombotic therapy has reduced the risk of blood clots in leg veins (also known as deep-vein thrombosis or DVT), a condition that can lead to death from pulmonary embolism (a clot that blocks an artery to the lungs) by more than 70 percent. And most importantly,
  • it has markedly reduced death from heart attacks, the risk of stroke in people with heart irregularities (atrial fibrillation), and the risk of major stroke in patients with mini-strokes.

Antithrombotic Therapy

This article was published in December 2008 as part of the special ASH anniversary brochure, 50 Years in Hematology: Research That Revolutionized Patient Care.

Normally, blood flows through our arteries and veins smoothly and efficiently, but if a clot, or thrombus, blocks the smooth flow of blood, the result – called thrombosis – can be serious and even cause death. Diseases arising from clots in blood vessels include heart attack and stroke, among others. These disorders collectively are the most common cause of death and disability in the developed world. We now have an array of drugs that can be used to prevent and treat thrombosis – and there are more on the way – but this was not always the case.

Classes of Antithrombotic Drugs

Image Source: http://www.hematology.org/About/History/50-Years/1523.aspx

The most important components of a thrombus are fibrin and platelets. Fibrin is a protein that forms a mesh that traps red blood cells, while platelets, a type of blood cell, form clumps that add to the mass of the thrombus. Both fibrin and platelets stabilize the thrombus and prevent it from falling apart. Fibrin is the more important component of clots that form in veins, and platelets are the more important component of clots that form in arteries where they can cause heart attacks and strokes by blocking the flow of blood in the heart and brain, respectively, although fibrin plays an important role in arterial thrombosis as well.

There are two classes of antithrombotic drugs: anticoagulants and antiplatelet drugs. Anticoagulants slow down clotting, thereby reducing fibrin formation and preventing clots from forming and growing. Antiplatelet agents prevent platelets from clumping and also prevent clots from forming and growing.

Anticoagulant Drugs

The anticoagulants heparin and dicumarol were discovered by chance, long before we understood how they worked. Heparin was first discovered in 1916 by a medical student at The Johns Hopkins University who was investigating a clotting product from extracts of dog liver and heart. In 1939, dicumarol (the precursor to warfarin) was extracted by a biochemist at the University of Wisconsin from moldy clover brought to him by a farmer whose prize bull had bled to death after eating the clover.

Both of these anticoagulants have been used effectively to prevent clots since 1940. These drugs produce a highly variable anticoagulant effect in patients, requiring their effect to be measured by special blood tests and their dose adjusted according to the results. Heparin acts immediately and is given intravenously (through the veins). Warfarin is swallowed in tablet form, but its anticoagulant effect is delayed for days. Therefore, until recently, patients requiring anticoagulants who were admitted to a hospital were started on a heparin infusion and were then discharged from the hospital after five to seven days on warfarin.

In the 1970s, three different groups of researchers in Stockholm, London, and Hamilton, Ontario, began work on low-molecular-weight heparin (LMWH). LMWH is produced by chemically splitting heparin into one-third of its original size. It has fewer side effects than heparin and produces a more predictable anticoagulant response. By the mid 1980s, LMWH preparations were being tested in clinical trials, and they have now replaced heparin for most indications. Because LMWH is injected subcutaneously (under the skin) in a fixed dose without the need for anticoagulant monitoring, patients can now be treated at home instead of at the hospital.

With the biotechnology revolution has come genetically engineered “designer” anticoagulant molecules that target specific clotting enzymes. Anti-clotting substances and their DNA were also extracted from an array of exotic creatures (ticks, leeches, snakes, and vampire bats) and converted into drugs by chemical synthesis or genetic engineering. Structural chemists next began to fabricate small molecules designed to fit into the active component of clotting enzymes, like a key into a lock.

The first successful synthetic anticoagulants were fondaparinux and bivalirudin. Bivalirudin, a synthetic molecule based on the structure of hirudin (the anti-clotting substance found in leeches), is an effective treatment for patients with heart attacks. Fondaparinux is a small molecule whose structure is based on the active component of the much larger LMWH and heparin molecules. It has advantages over LMWH and heparin and has recently been approved by the FDA. Newer designer drugs that target single clotting factors and that can be taken by mouth are undergoing clinical testing. If successful, we will have safer and more convenient replacements for warfarin, the only oral anticoagulant available for more than 60 years.

Antiplatelet Drugs

Blood platelets are inactive until damage to blood vessels or blood coagulation causes them to explode into sticky irregular cells that clump together and form a thrombus. The first antiplatelet drug was aspirin, which has been used to relieve pain for more than 100 years. In the mid-1960s, scientists showed that aspirin prevented platelets from clumping, and subsequent clinical trials showed that it reduces the risk of stroke and heart attack. In 1980, researchers showed that aspirin in very low doses (much lower than that required to relieve a headache) blocked the production of a chemical in platelets that is required for platelet clumping. During that time, better understanding of the process of platelet clumping allowed the development of designer antiplatelet drugs directed at specific targets. We now have more potent drugs, such as clopidogrel, dipyridamole, and abciximab. These drugs are used with aspirin and effectively prevent heart attack and stroke; they also prolong the lives of patients who have already had a heart attack.

SOURCE 
Anticoagulation Drugs:
  • heparin (FONDAPARINUX HEPARIN (Calciparine, Hepathrom, Lipo-Hepin, Liquaemin, Panheprin)
  • warfarin – 4-HYDROXYCOUMARIN (Coumadin) WARFARIN (Athrombin-K, Panwarfin)
  • rivaroxaban (Xarelto)
  • dabigatran (Pradaxa)
  • apixaban (Eliquis)
  • edoxaban (Savaysa)
  • enoxaparin (Lovenox)
  • fondaparinux (Arixtra)
  • ARGATROBAN BIVALIRUDIN (Angiomax)
  • DALTEPARIN (Fragmin)
  • DROTRECOGIN ALFA (ACTIVATED PROTEIN C) (Xigris)
  • HIRUDIN (Desirudin)
  • LEPIRUDIN (Refludan)
  • XIMELAGATRAN (Exanta)

ANTIDOTES

  • PHYTONADIONE (Vitamin K1)
  • PROTAMINE SULFATE AMINOCAPROIC ACID (EACA) (generic, Amicar) (in bleeding disorders)
Antiplatelet Drugs
  • ACETYL SALICYLIC ACID (aspirin) 
  • clopidogrel (Plavix)
  • dipyridamole (Persantine)
  • abciximab (Centocor)
  • EPTIFIBATIDE (Integrilin)
  • TICLOPIDINE (Ticlid)
  • TIROFIBAN (Aggrastat)

THROMBOLYTICS

  1. ANISTREPLASE (APSAC; Eminase)
  2. STREPTOKINASE (Streptase, Kabikinase)
  3. TISSUE PLASMINOGEN ACTIVATORS (tPAs):
  • ALTEPLASE (Activase),
  • RETEPLASE (Retavase),
  • TENECTEPLASE (TNKase)
  • UROKINASE (Abbokinase)

Fibrinolytic Drugs

Fibrinolytic therapy is used in selected patients with venous thromboembolism. For example, patients with massive or submassive PE can benefit from systemic or catheter-directed fibrinolytic therapy. The latter can also be used as an adjunct to anticoagulants for treatment of patients with extensive iliofemoral-vein thrombosis.

Arterial and venous thrombi are composed of platelets and fibrin, but the proportions differ.

  • Arterial thrombi are rich in platelets because of the high shear in the injured arteries. In contrast,
  • venous thrombi, which form under low shear conditions, contain relatively few platelets and are predominantly composed of fibrin and trapped red cells.
  • Because of the predominance of platelets, arterial thrombi appear white, whereas venous thrombi are red in color, reflecting the trapped red cells.

SOURCE

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Reporter and Curator: Dr. Sudipta Saha, Ph.D.

 

A heart-healthy diet has been the basis of atherosclerotic cardiovascular disease (ASCVD) prevention and treatment for decades. The potential cardiovascular (CV) benefits of specific individual components of the “food-ome” (defined as the vast array of foods and their constituents) are still incompletely understood, and nutritional science continues to evolve.

 

The scientific evidence base in nutrition is still to be established properly. It is because of the complex interplay between nutrients and other healthy lifestyle behaviours associated with changes in dietary habits. However, several controversial dietary patterns, foods, and nutrients have received significant media exposure and are stuck by hype.

 

Decades of research have significantly advanced our understanding of the role of diet in the prevention and treatment of ASCVD. The totality of evidence includes randomized controlled trials (RCTs), cohort studies, case-control studies, and case series / reports as well as systematic reviews and meta-analyses. Although a robust body of evidence from RCTs testing nutritional hypotheses is available, it is not feasible to obtain meaningful RCT data for all diet and health relationships.

 

Studying preventive diet effects on ASCVD outcomes requires many years because atherosclerosis develops over decades and may be cost-prohibitive for RCTs. Most RCTs are of relatively short duration and have limited sample sizes. Dietary RCTs are also limited by frequent lack of blinding to the intervention and confounding resulting from imperfect diet control (replacing 1 nutrient or food with another affects other aspects of the diet).

 

In addition, some diet and health relationships cannot be ethically evaluated. For example, it would be unethical to study the effects of certain nutrients (e.g., sodium, trans fat) on cardiovascular disease (CVD) morbidity and mortality because they increase major risk factors for CVD. Epidemiological studies have suggested associations among diet, ASCVD risk factors, and ASCVD events. Prospective cohort studies yield the strongest observational evidence because the measurement of dietary exposure precedes the development of the disease.

 

However, limitations of prospective observational studies include: imprecise exposure quantification; co-linearity among dietary exposures (e.g., dietary fiber tracks with magnesium and B vitamins); consumer bias, whereby consumption of a food or food category may be associated with non-dietary practices that are difficult to control (e.g., stress, sleep quality); residual confounding (some non-dietary risk factors are not measured); and effect modification (the dietary exposure varies according to individual/genetic characteristics).

 

It is important to highlight that many healthy nutrition behaviours occur with other healthy lifestyle behaviours (regular physical activity, adequate sleep, no smoking, among others), which may further confound results. Case-control studies are inexpensive, relatively easy to do, and can provide important insight about an association between an exposure and an outcome. However, the major limitation is how the study population is selected or how retrospective data are collected.

 

In nutrition studies that involve keeping a food diary or collecting food frequency information (i.e., recall or record), accurate memory and recording of food and nutrient intake over prolonged periods can be problematic and subject to error, especially before the diagnosis of disease.

 

The advent of mobile technology and food diaries may provide opportunities to improve accuracy of recording dietary intake and may lead to more robust evidence. Finally, nutrition science has been further complicated by the influences of funding from the private sector, which may have an influence on nutrition policies and practices.

 

So, the future health of the global population largely depends on a shift to healthier dietary patterns. Green leafy vegetables and antioxidant suppliments have significant cardio-protective properties when consumed daily. Plant-based proteins are significantly more heart-healthy compared to animal proteins.

 

However, in the search for the perfect dietary pattern and foods that provide miraculous benefits, consumers are vulnerable to unsubstantiated health benefit claims. As clinicians, it is important to stay abreast of the current scientific evidence to provide meaningful and effective nutrition guidance to patients for ASCVD risk reduction.

 

Available evidence supports CV benefits of nuts, olive oil and other liquid vegetable oils, plant-based diets and plant-based proteins, green leafy vegetables, and antioxidant-rich foods. Although juicing may be of benefit for individuals who would otherwise not consume adequate amounts of fresh fruits and vegetables, caution must be exercised to avoid excessive calorie intake. Juicing of fruits / vegetables with pulp removal increases calorie intake. Portion control is necessary to avoid weight gain and thus cardiovascular health.

 

There is currently no evidence to supplement regular intake of antioxidant dietary supplements. Gluten is an issue for those with gluten-related disorders, and it is important to be mindful of this in routine clinical practice; however, there is no evidence for CV or weight loss benefits, apart from the potential caloric restriction associated with a gluten free diet.

 

References:

 

https://www.ncbi.nlm.nih.gov/pubmed/28254181

 

https://www.sciencedirect.com/science/article/pii/S0735109713060294?via%3Dihub

 

http://circ.ahajournals.org/content/119/8/1161

 

http://refhub.elsevier.com/S0735-1097(17)30036-0/sref6

 

https://www.scopus.com/record/display.uri?eid=2-s2.0-0031709841&origin=inward&txGid=af40773f7926694c7f319d91efdcd40c

 

https://www.magonlinelibrary.com/doi/10.12968/hosp.2000.61.4.1875

 

https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2548255

 

https://pharmaceuticalintelligence.com/2018/05/31/supplements-offer-little-cv-benefit-and-some-are-linked-to-harm-in-j-am-coll-cardiol/

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Experimental Therapy (Left inter-atrial shunt implant device) for Heart Failure: Expert Opinion on a Preliminary Study on Heart Failure with preserved Ejection Fraction 

 

Article Curator: Aviva Lev-Ari, PhD, RN

 

UPDATED on 2/12/2019

Almost 25% of HFrEF patients prescribed drugs that could worsen their condition

Prescription of Potentially Harmful Drugs in Young Adults With Heart Failure and Reduced Ejection Fraction

Paulino A. Alvarez, MD'Correspondence information about the author MD Paulino A. Alvarez

,

Chau N Truong, MPH

,

Alexandros Briasoulis, MD PhD

,

Cecilia Ganduglia-Cazaban, MD PhD

The selection of medications for patients with multiple conditions (co-morbidities) always raises conflicts. This is true in general, and especially true for patients with heart failure. 

For example, patients with heart failure with reduced ejection fraction (HFrEF) have increased risk of atrial fibrillation, whereby sustained rapid ventricular response may worsen the failure due to tachycardiomyopathy. In essence, sustained high heatrates deplete supplies and weaken the heart, which can take months of controlled rates to recover.  

Medications to control the rate are problematic. Digoxin increases the death rate. Beta blockers and diltiazem decrease the heartrate but also decrease contractility (EF), and in combination may stop the heart (complete heart clock, cardiac arrest). Anti-arrhythmic agents also decrease contractility. Use of beta blockers is encouraged because benefits often outweigh the harm, though in some cases the decline in contractility results in unacceptably low blood pressure. Some patients with rate control issues do not tolerate beta blockers but do better on diltiazem instead. Thus the list of medications that may worsen heart failure constitute “relative contraindications” which means concerning but still possibly useful. 

In other words, some of the medications that may worsen ejection fraction have net benefit, and may be used with caution. 

Non-steroidal anti inflammatory agents (NSAIDs) are another example.  They relieve pain and add function to patients limited by arthritis.  High dose ibuprofen tapered over one month can stop pericarditis, as an alternative to colchicine which may be limited by causing intractable diarrhea. Nonsteroidal anti-inflammatory drugs (NSAIDs) decrease prostaglandin synthesis and, thus, may precipitate fluid retention in patients with heart failure. They also increase blood pressure, impair renal function and promote thrombosis (clotting). Use of NSAIDS has not been shown to curtail joint damage to joints, and daily use for 18 months or more promotes coronary disease. Overall, NSAIDs appear to be over utilized. 

The high incidence of use of medications that may cause or worsen reduced EF heart failure is a concern of caution.  Such use merits continual monitoring for net harm versus benefit on an individual basis.  The study in AJC documenting the high incidence of use of medications that worsen heart failure in patients already known to have reduced ejection fraction is helpful as a reminder of caution highlighting the importance of individualizing medication choices, but should not be rigidly interpreted as absolute contraindication or presumed error. 

SOURCE

From: Justin MDMEPhD <jdpmdphd@gmail.com>

Date: Tuesday, February 12, 2019 at 7:53 AM

To: Aviva Lev-Ari <aviva.lev-ari@comcast.net>

Subject: Re: Almost 25% of HFrEF patients prescribed drugs that could worsen their condition

 

UPDATED on 1/15/2019

 

Andrew Perry, MD, interviews John Gorcsan III, MD

In this episode, Andrew Perry, MD, discusses the utility of ejection fraction (EF) with John Gorcsan III, MD, an expert in echocardiography and strain imaging at Washington University School of Medicine in St. Louis.

They explore how EF came to be used in clinical practice, the importance of it in heart failure and the variation in measurement. The interview also covers strain imaging and what it adds to ejection fraction, particularly in the setting of severe mitral regurgitation.

UPDATED on 1/9/2019

Source: JACC Heart Fail
Curated by: Jenny Blair, MD
January 08, 2019

Takeaway

  • In heart failure (HF) with reduced ejection fraction (HFrEF), a drop in pro-B-type natriuretic peptide (NT-proBNP) to <1000 mg/mL reflects reverse remodeling and improved ejection fraction (EF).
  • Authors suggest that response to treatment based on change in NT-proBNP might outweigh treatment strategy.

Why this matters

  • Whether lower NT-proBNP levels reflect changes in cardiac structure and function has been unclear.

Key results

  • 12-month changes with guided therapy vs without:
    • No significant between-group differences in left ventricular (LV) end-systolic volume index (ESVi), NT-proBNP, EF.
  • Changes among subgroup whose NT-proBNP fell to <1000 pg/mL (n=52):
    • ESVi and end-diastolic volume index (EDVi) reductions: 17.3 and 15.7 mL/m2, respectively;
    • EF: 9.9%±8.8% vs 2.9%±7.9% in nontarget achievers (P<.001);
    • Death or HF hospitalization: 0% vs 30% in nontarget achievers (P<.001);
    • Greater improvement in global longitudinal strain, less mitral regurgitation.
  • Greater reduction in NT-proBNP correlated with significantly greater EF, ESVi, EDVi improvements.

Study design

  • Randomized parallel-group multicenter GUIDE-IT Echo Substudy.
  • 268 adults with HFrEF, EF ≤40%, NT-proBNP >2000 pg/mL randomly assigned to NT-proBNP-guided therapy vs usual care.
  • Outcome: 12-month change in LV ESVi on echocardiography.
  • Funding: Roche Diagnostics.

Limitations

  • Duration of NT-proBNP <1000 not assessed.

SOURCE

http://univadis.com/player/ymdmniqsi?m=unv_eml_essentials_enl_v4-q42018_20190109&partner=unl&rgid=5wrwznernxgefmacwqyebgmyb&ts=2019010900&o=tile_1_id&utm_source=Retention&utm_medium=newsletter&utm_campaign=unv_eml_essentials_enl_v4-q42018_20190109_01

Expert Opinion by Cardiologist Justin D. Pearlman MD PhD FACC

 

Pearls From: Ted Feldman, MD – A glimmer of hope for HFpEF treatment?

Evanston Hospital in Illinois

by Nicole Lou, Contributing Writer, MedPage Today

SOURCE ARTICLE

https://www.medpagetoday.com/cardiology/chf/72759?xid=nl_mpt_DHE_2018-05-09

WATCH VIDEO

https://www.medpagetoday.com/cardiology/chf/72759?xid=nl_mpt_DHE_2018-05-09

 

Heart Failure with preserved Ejection Fraction (or HFpEF) – Experimental Therapy: Inter-atrial shunt implantable device for relieving pressure overload and improve the prognosis of patients with a 50% ejection fraction

vs

Heart Failure with reduced Ejection Fraction (HFrEF)

 

  • HFpEF is similar in frequency and sadly, similar in prognosis to heart failure with reduced ejection fraction, and everybody thinks about the EF 20% or 30% patient as having a poor prognosis and doesn’t realize that the EF 40% or 45% or 50% patient with clinical heart failure has the same prognosis.
  • Patients with mitral stenosis and elevated left atrial pressure, which is the genesis of HFpEF, if they had an ASD historically, this decompressed the left atrium and they presented much, much later in the course of the disease with any signs of heart failure.
  • Inspiration for design of the Left inter-atrial shunt implant device

Minimally invasive transcatheter closure is the primary treatment option for secundum atrial septal defects (ASD). The AMPLATZER™ Septal Occluder is the proven standard of care in transcatheter ASD closure

  • Left inter-atrial shunt implant device, Dr. Ted Feldman calls IASD.

It’s like an ASD occluder, a little nitinol disc, but it has a hole in the middle. We did some baseline hemodynamic modeling using a simulator and calculated that we would get a small shunt with an eight millimeter opening, that that would be enough to reduce left atrial pressure overload during exercise without overloading the right side of the heart, without creating too big a shunt.

Preliminary results: We found that peak exercise wedge pressure was significantly decreased in the patients with the device compared to those without a shunt. We found that the shunt ratio, the amount of flow across the shunt was a Qp:Qs, pulmonary to systemic flow ratio, of 1.2 preserved at 30 days and 6 months and that most of these patients feel better.

Ted Feldman, MD, Evanston Hospital in Illinois

The mechanism, I think we’ve established, that we do decompress the left atrium with exertion and now we need to demonstrate that the clinical outcomes in a larger population are robust enough to carry this into practice.

Expert Opinion by Cardiologist Justin D. Pearlman MD PhD FACC

  • The assertion of “no treatment for HFpEF” (elevated left ventricular diastolic filling pressure) does not give credit to evidence and support for benefit from triple therapy of beta blocker, acei/arb/arni, and aldosterone inhibitor, plus tight blood pressure control and additional afterload reduction if valve leaks contribute to the elevated diastolic filling pressures.
  • It is an interesting proposition to induce an 8 mm intra-atrial septum (IAS) shunt, which may indeed unload high pressure in the left atrium and hence unload the left ventricle during diastole (when the mitral valve is open so the left ventricle and left atrium equalize pressures) if patients are very carefully selected and do not have high pressures in the right atrium. 
  • However, elevated left ventricular pressure is associated with reduced compliance (stiffness) of the left ventricle, for example due to high blood pressure, muscle hypertrophy and fibrosis. Adverse consequences include not only the high pressure which can back up to the lungs, making them boggy and therefore impair oxygen uptake resulting in shortness of breath worse laying down whereby more lung area is affected. The “back pressure” also promotes hepatic congestion and leg swelling. Each of those features of “diastolic failure” which underlies “HFpEF” may benefit from the proposed shunt if right atrial pressures are low, with or without preserved ejection fraction (pEF). However, there is an additional adverse consequence of a stiff left ventricle called “filling dependence” – if pressure is relieved, the left ventricle may under fill, reducing stroke volume and blood pressure, cardiac output (stroke volume times heart rate), thereby reducing organ perfusion. Low blood pressure with lightheaded spells is a common consequence. Over time, metarterioles to the brain can adjust to accommodate lower pressures. The kidneys as well as the brain are very sensitive to adequacy of cardiac output. A marked decline in renal function due to “pre-renal azotemia” is a common consequence that can limit any approach at lowering the diastolic filling pressure, which is seen commonly with use of diuretics to lower pressures.
  • The small opening is intended to allow pressure unloading without clots crossing over, but may still pose a risk for paradoxical emboli, which have been associated with
  1. visual field cuts,
  2. TIA and
  3. migraine headaches

Paradoxical Embolism

Updated: Jun 10, 2016
  • Author: Igor A Laskowski, MD; Chief Editor: Vincent Lopez Rowe, MD  more…
 Background

The clinical manifestations of paradoxical embolism (PDE) are nonspecific, [1and the diagnosis is difficult to establish. Patients with PDE may present with neurologic abnormalities or features suggesting arterial embolism. The disease starts with the formation of emboli within the venous system, which traverse a patent foramen ovale (PFO) and enter the systemic circulation. [234PFOs have been found on autopsy in up to 35% of the healthy population.

PDE originates in the veins of the lower extremities and occasionally in the pelvic veins. Emboli may be of various types, such as clots, air, tumor, fat, and amniotic fluid. [5Septic emboli have led to brain abscesses. Projectile embolization is rare (eg, from a shotgun pellet).

Management of PDE is both medical and surgical in nature. PDE is considered the major cause of cerebral ischemic events in young patients. On rare occasions, it may occlude the pelvic aortic bifurcation. The largest documented thrombus in a PFO (impending PDE) was 25 cm in length.

PDE is confirmed by the presence of thrombus within an intracardiac defect on contrast echocardiography or at autopsy. It may be presumed in the presence of arterial embolism with no evidence of left-side circulation thrombus, deep venous thrombosis (DVT) with or without pulmonary embolism (PE), and right-to-left shunting through an intracardiac communication, commonly the PFO. [6]

SOURCE for Paradoxical Embolism

https://emedicine.medscape.com/article/460607-overview

 

SOURCE for Dr. Pearlman’s Expert Opinion

From: Justin MDMEPhD <jdpmdphd@gmail.com>

Date: Wednesday, May 9, 2018 at 2:25 PM

To: Aviva Lev-Ari <AvivaLev-Ari@alum.berkeley.edu>

Cc: “Dr. Larry Bernstein” <larry.bernstein@gmail.com>

Subject: Re: WHICH of our Heart Failure ARTICLES I should UPDATE with the following Pearls From: Ted Feldman, MD | Medpage Today

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