Therapeutic Advances In Cardiovascular Disease[JOURNAL]
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200 papers
6-minute walking test: a useful tool in the management of heart failure patients.
Giannitsi S, Bougiakli M, Bechlioulis A … +3 more , Kotsia A, Michalis LK, Naka KK
Ther Adv Cardiovasc Dis · 2019 · PMID 31441375 · Full text
Reduced functional ability and exercise tolerance in patients with heart failure (HF) are associated with poor quality of life and a worse prognosis. The 6-minute walking test (6MWT) is a widely available and well-tolera...
Reduced functional ability and exercise tolerance in patients with heart failure (HF) are associated with poor quality of life and a worse prognosis. The 6-minute walking test (6MWT) is a widely available and well-tolerated test for the assessment of the functional capacity of patients with HF. Although the cardiopulmonary exercise test (a maximal exercise test) remains the gold standard for the evaluation of exercise capacity in patients with HF, the 6MWT (submaximal exercise test) may provide reliable information about the patient's daily activity. The current review summarizes the value of 6MWT in patients with HF and identifies its usefulness and limitations in everyday clinical practice in populations of HF. We aimed to investigate potential associations of 6MWD with other measures of functional status and determinants of 6MWD in patients with HF as well as to review its prognostic role and changes to various interventions in these patients.
The place of ARBs in heart failure therapy: is aldosterone suppression the key?
Markan U, Pasupuleti S, Pollard CM … +3 more , Perez A, Aukszi B, Lymperopoulos A
Ther Adv Cardiovasc Dis · 2019 · PMID 31401939 · Full text
Since the launch of the first orally available angiotensin II (AngII) type 1 receptor (ATR) blocker (ARB) losartan (Cozaar) in the late 1990s, the class of ARBs (or 'sartans', short for Angiotensin-RecepTor-ANtagonistS)...
Since the launch of the first orally available angiotensin II (AngII) type 1 receptor (ATR) blocker (ARB) losartan (Cozaar) in the late 1990s, the class of ARBs (or 'sartans', short for Angiotensin-RecepTor-ANtagonistS) quickly expanded to include candesartan, eprosartan, irbesartan, valsartan, telmisartan, and olmesartan. All ARBs have high affinity for the AT receptor, expressed in various tissues, including smooth muscle cells, heart, kidney, and brain. Since activation of ATR, the target of these drugs, leads, among other effects, to vascular smooth muscle cell growth, proliferation and contraction, activation of fibroblasts, cardiac hypertrophy, aldosterone secretion from the adrenal cortex, thirst-fluid intake (hypervolemia), etc., the ARBs are nowadays one of the most useful cardiovascular drug classes used in clinical practice. However, significant differences in their pharmacological and clinical properties exist that may favor use of particular agents over others within the class, and, in fact, two of these drugs, candesartan and valsartan, continuously appear to distinguish themselves from the rest of the 'pack' in recent clinical trials. The reason(s) for the potential superiority of these two agents within the ARB class are currently unclear but under intense investigation. The present short review gives an overview of the clinical properties of the ARBs currently approved by the United States Food and Drug Administration, with a particular focus on candesartan and valsartan and the areas where these two drugs seem to have a therapeutic edge. In the second part of our review, we outline recent data from our laboratory (mainly) on the molecular effects of the ARB drugs on aldosterone production and on circulating aldosterone levels, which may underlie (at least in part) the apparent clinical superiority of candesartan (and valsartan) over most other ARBs currently in clinical use.
Influence of model-predicted rivaroxaban exposure and patient characteristics on efficacy and safety outcomes in patients with acute coronary syndrome.
Zhang L, Yan X, Nandy P … +9 more , Willmann S, Fox KAA, Berkowitz SD, Sharma A, Hermanowski-Vosatka A, Schmidt S, Weitz JI, Garmann D, Peters G
Ther Adv Cardiovasc Dis · 2019 · PMID 31364490 · Full text
BACKGROUND: This analysis aimed to evaluate the impact of rivaroxaban exposure and patient characteristics on efficacy and safety outcomes in patients with acute coronary syndrome (ACS) and to determine whether therapeut...
BACKGROUND: This analysis aimed to evaluate the impact of rivaroxaban exposure and patient characteristics on efficacy and safety outcomes in patients with acute coronary syndrome (ACS) and to determine whether therapeutic drug monitoring might provide additional information regarding rivaroxaban dose, beyond what patient characteristics provide. METHODS: A exposure-response analysis was conducted using data from the phase III ATLAS ACS 2 Thrombolysis in Myocardial Infarction (TIMI) 51 study, in which 15,526 randomized ACS patients received rivaroxaban (2.5 mg or 5 mg twice daily) or placebo for a mean of 13 months (maximum follow up: 31 months). A multivariate Cox model was used to correlate individual predicted rivaroxaban exposures and patient characteristics with time-to-event clinical outcomes. RESULTS: For the incidence of myocardial infarction (MI), ischemic stroke, or nonhemorrhagic cardiovascular death, hazard ratios (HRs) for steady-state maximum plasma concentration (C) in the 5th and 95th percentiles the median were statistically significant but close to 1 for both rivaroxaban doses. For TIMI major bleeding events, a statistically significant association was observed with C [HR, 1.08; 95% CI, 1.06-1.11 (95th percentile median, 2.5 mg twice daily)], sex [HR, 0.56; 95% CI, 0.38-0.84 (female male)], and previous revascularization [HR, 0.62; 95% CI, 0.44-0.87 (no yes)]. CONCLUSIONS: The shallow slopes of the exposure-response relationships and the lack of a clear therapeutic window render it unlikely that therapeutic drug monitoring in patients with ACS would provide additional information regarding rivaroxaban dose beyond that provided by patient characteristics.
Predicting outcomes in patients with cancer and atrial fibrillation.
Gutierrez A, Patell R, Rybicki L … +1 more , Khorana AA
Ther Adv Cardiovasc Dis · 2019 · PMID 31319783 · Full text
BACKGROUND: The role of cancer-specific factors for ischemic stroke and mortality in patients with cancer and atrial fibrillation (AF) is unknown. We evaluated the utility of a previously validated risk tool for venous t...
BACKGROUND: The role of cancer-specific factors for ischemic stroke and mortality in patients with cancer and atrial fibrillation (AF) is unknown. We evaluated the utility of a previously validated risk tool for venous thromboembolism (VTE) in cancer outpatients [Khorana score (KS)] in predicting stroke and mortality in cancer patients with AF. METHODS: We conducted a retrospective cohort study of patients with cancer and AF at the Cleveland Clinic from 2008 to 2014. Outcomes, CHADS2, CHA2DS2-VASc, and KS scores were calculated from date of cancer diagnosis. Prognostic factors were identified with Fine and Gray regression (for stroke) or Cox proportional hazards analysis (for mortality). RESULTS: The study population comprised 1181 patients. Genitourinary (19%), lung (18%), and gastrointestinal (13%) were the most frequent cancers. Overall, 67% had CHADS2 ⩾ 2, 57% had an intermediate KS (1-2), and 7% high KS (⩾3). Median follow up was 26.5 months (range 0.03-76). At a median of 8.2 months (range 0-61), 45 patients (3.8%) developed a stroke and 418 (35%) died. In multivariable analysis a high KS (HR 4.5, 95% CI 3.2-6.3, < 0.001) was associated with a quadruple risk of death and every point increase in CHADS2 score had a 20% increased risk of death (HR 1.19, 95% CI 1.1-1.2, < 0.001). The addition of KS did not improve risk stratification for ischemic stroke to CHADS2. CONCLUSION: In patients with cancer and AF, CHADS2 and CHA2DS2-VASc but not KS were predictive of ischemic stroke. A high KS represented a unique predictor of mortality beyond traditional risk scores.
Inflammation, depression and cardiovascular disease in women: the role of the immune system across critical reproductive events.
Mattina GF, Van Lieshout RJ, Steiner M
Ther Adv Cardiovasc Dis · 2019 · PMID 31144599 · Full text
Women are at increased risk for developing depression and cardiovascular disease (CVD) across the lifespan and their comorbidity is associated with adverse outcomes that contribute significantly to rates of morbidity and...
Women are at increased risk for developing depression and cardiovascular disease (CVD) across the lifespan and their comorbidity is associated with adverse outcomes that contribute significantly to rates of morbidity and mortality in women worldwide. Immune-system activity has been implicated in the etiology of both depression and CVD, but it is unclear how inflammation contributes to sex differences in this comorbidity. This narrative review provides an updated synthesis of research examining the association of inflammation with depression and CVD, and their comorbidity in women. Recent research provides evidence of pro-inflammatory states and sex differences associated with alterations in the hypothalamic-pituitary-adrenal axis, the renin-angiotensin-aldosterone system and the serotonin/kynurenine pathway, that likely contribute to the development of depression and CVD. Changes to inflammatory cytokines in relation to reproductive periods of hormonal fluctuation (i.e. the menstrual cycle, perinatal period and menopause) are highlighted and provide a greater understanding of the unique vulnerability women experience in developing both depressed mood and adverse cardiovascular events. Inflammatory biomarkers hold substantial promise when combined with a patient's reproductive and mental health history to aid in the prediction, identification and treatment of the women most at risk for CVD and depression. However, more research is needed to improve our understanding of the mechanisms underlying inflammation in relation to their comorbidity, and how these findings can be translated to improve women's health.
A comprehensive review of chronic heart failure pharmacotherapy treatment approaches in African Americans.
Tillman F, Kim J, Makhlouf T … +1 more , Osae L
Ther Adv Cardiovasc Dis · 2019 · PMID 31092128 · Full text
BACKGROUND: Our aim was to review the published literature evaluating treatment approaches for chronic heart failure (HF), notably as it relates to African American patients. METHOD: We undertook a comprehensive database...
BACKGROUND: Our aim was to review the published literature evaluating treatment approaches for chronic heart failure (HF), notably as it relates to African American patients. METHOD: We undertook a comprehensive database search (1986-2017) of PubMed, EMBASE, and Ovid/MEDLINE utilizing terms 'African American', 'black', 'chronic heart failure', 'heart failure', 'medication', 'chronic therapy', and 'clinical trials'. Additional notable studies were obtained from ClinicalTrials.gov . Studies published in English that examine treatment modalities of chronic HF in African American and non-African American patients were included. RESULTS: Examples of current gaps worthy of investigation include whether to maximize thiazides and calcium-channel blockers prior to adding renin-angiotensin system (RAS) inhibitors or beta blockers in HF with preserved ejection fraction; whether hydralazine/isosorbide dinitrate (ISDN) should be initiated during earlier HF stages; whether to prioritize hydralazine/ISDN over other agents such as RAS inhibitors; varying response of African Americans to different agents within drug classes; and the role of mineralocorticoid receptor antagonists. CONCLUSION: Further studies are needed in order for consensus guidelines to clarify how best to treat this population.
Dysregulation of proangiogeneic factors in pressure-overload left-ventricular hypertrophy results in inadequate capillary growth.
Zeriouh M, Sabashnikov A, Tenbrock A … +10 more , Neef K, Merkle J, Eghbalzadeh K, Weber C, Liakopoulos OJ, Deppe AC, Stamm C, Cowan DB, Wahlers T, Choi YH
Ther Adv Cardiovasc Dis · 2019 · PMID 31088231 · Full text
BACKGROUND: Pressure-overload left-ventricular hypertrophy (LVH) is an increasingly prevalent pathological condition of the myocardial muscle and an independent risk factor for a variety of cardiac diseases. We investiga...
BACKGROUND: Pressure-overload left-ventricular hypertrophy (LVH) is an increasingly prevalent pathological condition of the myocardial muscle and an independent risk factor for a variety of cardiac diseases. We investigated changes in expression levels of proangiogeneic genes in a small animal model of LVH. METHODS: Myocardial hypertrophy was induced by transaortic constriction (TAC) in C57BL/6 mice and compared with sham-operated controls. The myocardial expression levels of vascular endothelial growth factor (VEGF), its receptors (KDR and FLT-1), stromal-cell-derived factor 1 (SDF1) and the transcription factors hypoxia-inducible factor-1 and 2 (HIF1 and HIF2) were analyzed by quantitative polymerase chain reaction over the course of 25 weeks. Histological sections were stained for caveolin-1 to visualize endothelial cells and determine the capillary density. The left-ventricular morphology and function were assessed weekly by electrocardiogram-gated magnetic resonance imaging. RESULTS: The heart weight of TAC animals increased significantly from week 4 to 25 ( p = 0.005) compared with sham-treated animals. At 1 day after TAC, the expression of VEGF and SDF1 also increased, but was downregulated again after 1 week. The expression of HIF2 was significantly downregulated after 1 week and remained at a lower level in the subsequent weeks. The expression level of FLT-1 was also significantly decreased 1 week after TAC. HIF-1 and KDR showed similar changes compared with sham-operated animals. However, the expression levels of HIF1 after 4 and 8 weeks were significantly decreased compared with day 1. KDR changes were significantly decreased after 1, 2, 4, 8 and 25 weeks compared with week 3. After 4 weeks post-TAC, the size of the capillary vessels increased ( p = 0.005) while the capillary density itself decreased (TAC: 2143 ± 293 /mm versus sham: 2531 ± 321 /mm; p = 0.021). Starting from week 4, the left-ventricular ejection fraction decreased compared with controls ( p = 0.049). CONCLUSIONS: The decrease in capillary density in the hypertrophic myocardium appears to be linked to the dysregulation in the expression of proangiogeneic factors. The results suggest that overcoming this dysregulation may lead to reconstitution of capillary density in the hypertrophic heart, and thus be beneficial for cardiac function and survival.
Cardiotoxicity due to targeted anticancer agents: a growing challenge.
Shah CP, Moreb JS
Ther Adv Cardiovasc Dis · 2019 · PMID 30995890 · Full text
The emergence of various targeted anticancer agents has led us to uncharted territory secondary to their cardiotoxic potential with many burning questions, which in turn has led to the evolution of the cardio-oncology fi...
The emergence of various targeted anticancer agents has led us to uncharted territory secondary to their cardiotoxic potential with many burning questions, which in turn has led to the evolution of the cardio-oncology field. These targeted agents differ in their cardiovascular complication (CVC) potential even within the same class and it is very difficult to design screening tests that can predict CVCs. Moreover, there is a need for more research to answer many crucial questions, since these toxicities are unanticipated and can lead to poor overall survival of cancer patients. We still do not clearly understand the mechanism for such toxicity, risk factors, and natural history. A better understanding of the underlying risk factors and identification of biomarkers would help us develop protocols for appropriate monitoring strategies which in turn would help capture these toxicities at early stages. In this succinct review, we try to focus on CVC definition, summarize some published research, and point to areas of unmet need in this new field.
Comparative preclinical evaluation of a polymer-free sirolimus-eluting stent in porcine coronary arteries.
Sperling C, Waliszewski MW, Kherad B … +1 more , Krackhardt F
Ther Adv Cardiovasc Dis · 2019 · PMID 30803407 · Full text
BACKGROUND:: Polymer-free drug-eluting stents (DES) without permanent-polymer coating may be associated with rapid vessel healing, providing a rationale to reduce dual-antiplatelet therapy (DAPT). The aim of the current...
BACKGROUND:: Polymer-free drug-eluting stents (DES) without permanent-polymer coating may be associated with rapid vessel healing, providing a rationale to reduce dual-antiplatelet therapy (DAPT). The aim of the current study was to compare vessel healing of a polymer-free sirolimus-eluting stent (PF-SES), its bare metal stent (BMS) analogue to a permanent polymer-based sirolimus-eluting stent (SES) with proven effectiveness in porcine coronary arteries. MATERIAL AND METHODS:: An ultrathin-strut cobalt-chromium PF-SES, its BMS analogue and an SES with a permanent polymer were used to study vessel healing and their antistenotic potential. Stents were implanted in porcine coronary arteries for histopathologic analysis at 7, 28 and 180 days. In an additional in vitro study, the thrombogenicity of PF-SES was compared with a fluoropolymer-coated everolimus-eluting stent (EES) which demonstrated low stent thrombosis rates in numerous studies. RESULTS:: In the animal study, neointimal growth and injury scores were minimal and inflammation scores were low in the neointima and adventitia in all study groups. After 28 days, neointimal area was lowest in PF-SES when compared with SES and BMS (1.48 ± 0.55 mm² versus 2.43 ± 0.69 mm² versus 1.90 ± 0.85 mm², respectively, p < 0.05) and endothelialization of luminal surfaces was nearly complete in all groups, though SES show the least coverage with occasional adherent luminal inflammatory cells ( p > 0.05). At 180 days, neointimal area and thickness were most pronounced in SES ( p < 0.05) and comparable with BMS implantations, which were characterized by nearly completed vessel healing. PF-SES and BMS had complete endothelialization, absence of fibrin and sustained low inflammatory reaction when compared with the permanent polymer-based SES (inflammation score: PF-SES 0.41 ± 0.74 versus SES 2.52 ± 1.72 versus BMS 0.30 ± 0.65, respectively, p < 0.05 BMS versus SES). Granuloma formation and fibrin accumulation were most pronounced in SES but did not reach statistical significance, p > 0.05). In the in vitro thrombogenicity study, the PF-SES confirmed comparable antithrombogenic properties with regard to the parameters fibrin and platelet binding, and platelet aggregation when compared with the EES. CONCLUSIONS:: As compared with BMS, the ultrathin-strut cobalt-chromium PF-SES showed similar endothelialization at 28 days and comparable healing characteristics at 180 days efficacious inhibition of neointimal proliferation in porcine coronary arteries with low inflammation responses and a BMS-like endothelialization at 180 days. In addition, in an in vitro model, the PF-SES also confirmed low thrombogenicity as compared with the EES.
Serum copeptin might improve risk stratification and management of aortic valve stenosis: a review of pathophysiological insights and practical implications.
Yalta K, Palabiyik O, Gurdogan M … +1 more , Gurlertop Y
Ther Adv Cardiovasc Dis · 2019 · PMID 30803406 · Full text
Over recent decades, the prevalence of aortic valve stenosis (AVS) has been constantly increasing possibly owing to the aging of general population. Severe AVS as determined by an aortic valve area (AVA) of <1 cm has bee...
Over recent decades, the prevalence of aortic valve stenosis (AVS) has been constantly increasing possibly owing to the aging of general population. Severe AVS as determined by an aortic valve area (AVA) of <1 cm has been regarded as a serious clinical condition potentially associated with a variety of adverse outcomes, including sudden cardiac death (SCD). However, patients with severe AVS (in the absence of overt high-risk features) are usually evaluated and managed exclusively based on symptomatology or imperfect prognostic tools including exercise testing and biomarkers, with a potential risk of mismanagement, suggesting the need for further objective risk stratifiers in this setting. Within this context, copeptin (C-terminal pro-vasopressin), a novel neurohormone widely considered as the surrogate marker of the arginine-vasopressin (AVP) system, may potentially serve as a reliable prognostic and therapeutic guide (e.g. timing of aortic valvular intervention) in patients with severe AVS largely based on its hemodynamic, fibrogenic as well as autonomic implications in these patients. Accordingly, the present paper aims to discuss clinical and pathophysiological implications of copeptin in the setting of AVS along with a summary of biomarkers and other prognostic tools used in this setting.
An update on the CardioMEMS pulmonary artery pressure sensor.
Ayyadurai P, Alkhawam H, Saad M … +4 more , Al-Sadawi MA, Shah NN, Kosmas CE, Vittorio TJ
Ther Adv Cardiovasc Dis · 2019 · PMID 30803405 · Full text
Heart failure (HF) is one of the most important healthcare issues due to its prevalence, high morbidity and mortality, as well as its economic burden. A shift in the healthcare model towards reducing inpatient hospitaliz...
Heart failure (HF) is one of the most important healthcare issues due to its prevalence, high morbidity and mortality, as well as its economic burden. A shift in the healthcare model towards reducing inpatient hospitalizations might have a significant impact on HF-related costs and quality of life. Recently, wireless monitoring has begun to be an essential part of the management in the patient with HF. The CardioMEMS HF system is one of the best examples pertaining to the success in this field. This article will discuss the CardioMEMS HF system and the rationale behind its development.
High prevalence of exercise-induced ischemia in the asymptomatic limb of patients with apparently strictly unilateral symptoms and unilateral peripheral artery disease.
Henni S, Bauer P, Le Meliner T … +7 more , Hersant J, Papon X, Daligault M, Chretien JM, Ammi M, Picquet J, Abraham P
Ther Adv Cardiovasc Dis · 2019 · PMID 30803404 · Full text
BACKGROUND:: The prevalence of exercise-induced ischemia in the asymptomatic limb of patients with unilateral claudication based on history and treadmill evaluation, and with unilateral ipsilateral peripheral artery dise...
BACKGROUND:: The prevalence of exercise-induced ischemia in the asymptomatic limb of patients with unilateral claudication based on history and treadmill evaluation, and with unilateral ipsilateral peripheral artery disease (i.e ankle-to-brachial systolic pressure index <0.90) is unknown. METHODS:: We detected exercise-induced ischemia in the asymptomatic limb of patients with apparently unilateral claudication. Among 6059 exercise-oximetry tests performed in 3407 nondiabetic and 961 diabetic patients. We estimated the intensity of ischemia in the both limb (buttocks and calves) using the lowest minimum value of the decrease from rest of oxygen pressure (DROP; limb changes minus chest changes from rest), with significant ischemia defined as DROP lower than -15 mmHg. RESULTS:: We found 152 tests performed in 142 nondiabetic patients and 40 tests performed in 38 diabetic patients. The asymptomatic limb showed significant ischemia in 46.7% and 37.5% of the tests. Strictly unilateral exercise-induced claudication with apparently unilateral peripheral artery disease was rare (<4% of all tests). However, among these highly selected tests, significant ischemia was found in the asymptomatic limb in more than one-third of cases. CONCLUSION:: The asymptomatic limb of patients with peripheral artery disease should not be considered a normal limb.
Impact of renal function on mid-term outcomes in heart failure patients treated with tolvaptan.
Fujioka K, Mizuno S, Ichise T … +8 more , Matsui T, Hirase H, Yamaguchi M, Aoyama T, Yamagishi M, Fujino N, Kawashiri MA, Hayashi K
Ther Adv Cardiovasc Dis · 2019 · PMID 30803403 · Full text
BACKGROUND:: Although tolvaptan, an electrolyte-free water diuretic for congestive heart failure (HF), is reported to have no effect on long-term mortality or HF-related morbidity, there may exist some subgroups of patie...
BACKGROUND:: Although tolvaptan, an electrolyte-free water diuretic for congestive heart failure (HF), is reported to have no effect on long-term mortality or HF-related morbidity, there may exist some subgroups of patients who may receive beneficial effect of tolvaptan. The purpose of this study was to identify clinical factors associated with mid-term effect of tolvaptan on clinical outcomes of patients who discharged after acute HF. METHODS:: We retrospectively analyzed 140 patients (88 male; mean age, 77.1 ± 11.0 years) with acute HF who received tolvaptan (initial dose 8.6 ± 3.6 mg/day) during their hospitalization. They were divided into two groups according to how the tolvaptan was used at discharge; 77 in the tolvaptan-continued group and 63 in the discontinued group. RESULTS:: The Cox proportional hazards model revealed that eGFR was the only independent predictor for the occurrence of mid-term cardiac events (composite of re-hospitalization due to HF and all-cause death; aHR = 0.9870, p = 0.02597). The Kaplan-Meier survival curves of the two groups demonstrated no difference in cumulative event-free rates. In the subgroup with preserved renal function at admission (eGFR ⩾ 30 ml/min/1.73 m), the continuous use of tolvaptan increased composite events (aHR = 2.130, p = 0.02549). CONCLUSIONS:: The continuous use of tolvaptan after discharge did not affect mid-term cardiac events of HF overall but may be associated with increased cardiac events in the subgroup with preserved renal function. These findings suggest that the tolvaptan administration might need to be limited to treatment of in-hospital acute HF.
The effect of angiotensin-converting enzyme inhibitors on clinical outcomes in patients with ischemic cardiomyopathy and midrange ejection fraction: a post hoc subgroup analysis from the PEACE trial.
Alzahrani T, Tiu J, Panjrath G … +1 more , Solomon A
Ther Adv Cardiovasc Dis · 2018 Dec · PMID 30442080 · Full text
BACKGROUND:: There have been significant advances in the treatment of patients with cardiomyopathy with reduced ejection fraction (EF < 40%). However, there is a dearth of information in the treatment of patients with ca...
BACKGROUND:: There have been significant advances in the treatment of patients with cardiomyopathy with reduced ejection fraction (EF < 40%). However, there is a dearth of information in the treatment of patients with cardiomyopathy and midrange EF (40-50%). Current guidelines state to treat these patients similarly to patients with cardiomyopathy and preserved EF. Data from the Prevention of Events with Angiotensin-Converting Enzyme Inhibition (PEACE) trial were used to elucidate whether angiotensin-converting enzyme (ACE) inhibitors improve clinical outcomes in patients with ischemic cardiomyopathy and midrange EF. METHODS:: A post hoc subgroup analysis of the PEACE trial was conducted to evaluate the effect of ACE inhibitors in a subgroup of patients with ischemic cardiomyopathy and midrange EF (40-50%). A Chi-square test and a Student's t-test were used to examine and compare the binary and continuous variables of baseline characteristics and outcomes between experimental and comparison groups. RESULTS:: We studied a subgroup of patients from the PEACE trial with ischemic cardiomyopathy and midrange EF ( n = 2512 of 8290 total patients). Patients were assigned to either the interventional group ( n = 1247) or the placebo group ( n = 1265). There were no significant differences in baseline demographic and health characteristics between the two groups. During a total of 7 years (mean 4.7 years) of follow up, the risk of composite outcomes [all-cause mortality, nonfatal myocardial infarction, and stroke; relative risk (RR) 0.79, 95% confidence interval (CI) 0.63-0.98; p = 0.03] and all-cause mortality (RR 0.85, 95% CI 0.73-0.99; p = 0.03) was reduced in patients treated with trandolapril. CONCLUSION:: This study revealed the benefit of ACE inhibitors among patients with ischemic cardiomyopathy and midrange EF.
Remote post-conditioning and allopurinol reduce ischemia-reperfusion injury in an infra-renal ischemia model.
Brandão RI, Gomes RZ, Lopes L … +3 more , Linhares FS, Vellosa JCR, Paludo KS
Ther Adv Cardiovasc Dis · 2018 Dec · PMID 30295166 · Full text
BACKGROUND:: The aim of this study was to evaluate the effects of the antioxidant allopurinol and ischemic post-conditioning on the deleterious effects of ischemia followed by reperfusion (I/R) in a standardized model of...
BACKGROUND:: The aim of this study was to evaluate the effects of the antioxidant allopurinol and ischemic post-conditioning on the deleterious effects of ischemia followed by reperfusion (I/R) in a standardized model of ischemia involving infra-renal aortic occlusion in rats. METHODS:: The animals were randomly divided into five groups: (A) animals not subjected to ischemia; (B) animals subjected to 2 h of ischemia and reperfusion only once; (C) animals given an allopurinol dose by gavage, then subjected to 2 h of ischemia and reperfusion only once; (D) animals subjected to 2 h of ischemia and post-conditioning and (E) animals that received allopurinol, then subjected to 2 h of ischemia and post-conditioning. The blood samples and small intestine segments were harvested for analysis after 3 days. RESULTS:: The protective effects of the use of allopurinol and ischemic post-conditioning were observed by measuring aspartate aminotransferase, alanine aminotransferase and lactate levels. The benefits of post-conditioning were evident from the total antioxidant capacity and creatinine levels, but these could not ascertain any positive effects of allopurinol. The histological analysis of mesentery revealed that both methods were effective in minimizing the harmful effects of the ischemia and reperfusion process. CONCLUSION:: Individual protocols significantly reduced I/R systemic injuries, but no additional protection was observed when the two strategies were combined.
Impact of ascending aortic, hemiarch and arch repair on early and long-term outcomes in patients with Stanford A acute aortic dissection.
Merkle J, Sabashnikov A, Deppe AC … +15 more , Zeriouh M, Maier J, Weber C, Eghbalzadeh K, Schlachtenberger G, Shostak O, Djordjevic I, Kuhn E, Rahmanian PB, Madershahian N, Rustenbach C, Liakopoulos O, Choi YH, Kuhn-Régnier F, Wahlers T
Ther Adv Cardiovasc Dis · 2018 Dec · PMID 30295137 · Full text
BACKGROUND:: Stanford A acute aortic dissection (AAD) is a life-threatening emergency associated with major morbidity and mortality. The aim of this study was to compare outcomes of three different surgical approaches in...
BACKGROUND:: Stanford A acute aortic dissection (AAD) is a life-threatening emergency associated with major morbidity and mortality. The aim of this study was to compare outcomes of three different surgical approaches in patients with Stanford A AAD. METHODS:: From January 2006 to March 2015 a total of 240 consecutive patients with diagnosed Stanford A AAD underwent elective, isolated surgical aortic repair in our centre. Patients were divided into three groups according to the extent of surgical repair: isolated replacement of the ascending aorta, hemiarch replacement and total arch replacement. Patients were followed up for up to 9 years. After univariate analysis multinomial logistic regression was performed for subgroup analysis. Baseline characteristics and endpoints as well as long-term survival were analysed. RESULTS:: There were no statistically significant differences among the three groups in terms of demographics and preoperative baseline and clinical characteristics. Incidence of in-hospital stroke ( p = 0.034), need for reopening due to bleeding ( p = 0.031) and in-hospital mortality ( p = 0.017) increased significantly with the extent of the surgical approach. There was no statistical difference in terms of long-term survival ( p = 0.166) among the three groups. Applying multinomial logistic regression for subgroup analysis significantly higher odds for stroke ( p = 0.023), reopening for bleeding ( p = 0.010) and in-hospital mortality ( p = 0.009) for the arch surgery group in comparison to the ascending aorta surgery group as well as significantly higher odds for stroke ( p = 0.029) for the total arch surgery group in comparison to the hemiarch surgery group were identified. CONCLUSIONS:: With Stanford A AAD the incidence of perioperative complications increased significantly with the extent of the surgical approach. Subgroup analysis and long-term follow up in patients undergoing isolated ascending or hemiarch surgery showed a lower incidence of cerebrovascular events compared with surgery for total arch replacement.
Bleeding in patients receiving non-vitamin K oral anticoagulants: clinical trial evidence.
Bracey A, Shatila W, Wilson J
Ther Adv Cardiovasc Dis · 2018 Dec · PMID 30270775 · Full text
In optimizing anticoagulation therapy, it is essential to balance treatment efficacy with the major adverse effect of anticoagulant treatment, bleeding risk. This narrative review examines the efficacy and safety of the...
In optimizing anticoagulation therapy, it is essential to balance treatment efficacy with the major adverse effect of anticoagulant treatment, bleeding risk. This narrative review examines the efficacy and safety of the non-vitamin K antagonist oral anticoagulants (NOACs) dabigatran, rivaroxaban, apixaban, and edoxaban compared with standard anticoagulation or placebo. NOAC therapies provide equivalent to superior protection versus standard therapy, with similar or superior safety, and potential benefits in convenience. We will review the phase III evidence for each of the available NOACs in different antithrombotic indications, including atrial fibrillation (in the absence of significant mitral stenosis or mechanical heart valves); prophylaxis of venous thromboembolism (VTE) in patients undergoing orthopedic surgery; and acute and long-term treatment of VTE. Further, we will illustrate scenarios in which the evidence is stronger for a particular agent in the context of the overall positive safety and efficacy profile of NOACs in general. Limitations of the factor Xa inhibitors include the lack of a specific antidote in case of a bleeding emergency (an approved agent is available for reversing the effect of the direct thrombin inhibitor). We discuss the options for mitigating bleeding and describe the ongoing developments towards specific reversal agents. In conclusion, the available data for efficacy and safety, together with reliable pharmacokinetics obviating the need for regular monitoring, indicate that NOACs may offer substantial benefits for patients with nonvalvular atrial fibrillation or VTE.
Impact of meteorological conditions on the incidence of acute aortic dissection.
Majd P, Madershahian N, Sabashnikov A … +9 more , Weber C, Ahmad W, Weymann A, Heinen S, Merkle J, Eghbalzadeh K, Wippermann J, Brunkwall J, Wahlers T
Ther Adv Cardiovasc Dis · 2018 Dec · PMID 30244647 · Full text
BACKGROUND:: There is still much controversy about whether meteorological conditions influence the occurrence of acute aortic dissection (AAD). The aim of the present study was to investigate the possible correlation bet...
BACKGROUND:: There is still much controversy about whether meteorological conditions influence the occurrence of acute aortic dissection (AAD). The aim of the present study was to investigate the possible correlation between atmospheric pressure, temperature, lunar cycle and the event of aortic dissection in our patient population. METHODS:: The clinical data for 348 patients with AAD (73% type Stanford A) were confronted with the meteorological data provided by the Cologne weather station over the same period. RESULTS:: There were no statistically significant differences between meteorological parameters on days of AAD events compared with control days. A logistic regression model showed that air pressure (odds ratio [OR] 1.004, 95% confidence interval [CI] 0.991-1.017, p = 0.542), air temperature (OR 0.978, 95% CI 0.949-1.008, p = 0.145), season ( p = 0.918) and month of the event ( p = 0.175) as well as presence of full moon (OR 1.579, 95% CI 0.763-3.270, p = 0.219) were not able to predict AAD events. Also, no predictive power of meteorological data and season was found on analysing their impact on different types of AAD events. CONCLUSIONS:: Our study did not reveal any dependence of atmospheric pressure, air temperature or the presence of full moon on the incidence of different types of AAD.
Long-term outcome of elderly out-of-hospital cardiac arrest survivors as compared with their younger counterparts and the general population.
Hiemstra B, Bergman R, Absalom AR … +6 more , van der Naalt J, van der Harst P, de Vos R, Nieuwland W, Nijsten MW, van der Horst ICC
Ther Adv Cardiovasc Dis · 2018 Dec · PMID 30231773 · Full text
BACKGROUND:: Over the past decade, prehospital and in-hospital treatment for out-of-hospital cardiac arrest (OHCA) has improved considerably. There are sparse data on the long-term outcome, especially in elderly patients...
BACKGROUND:: Over the past decade, prehospital and in-hospital treatment for out-of-hospital cardiac arrest (OHCA) has improved considerably. There are sparse data on the long-term outcome, especially in elderly patients. We studied whether elderly patients benefit to the same extent compared with younger patients and at long-term follow up as compared with the general population. METHODS:: Between 2001 and 2010, data from all patients presented to our hospital after OHCA were recorded. Elderly patients (⩾75 years) were compared with younger patients. Neurological outcome was classified as cerebral performance category (CPC) at hospital discharge and long-term survival was compared with younger patients and predicted survival rates of the general population. RESULTS:: Of the 810 patients admitted after OHCA, a total of 551 patients (68%) achieved return of spontaneous circulation, including 125 (23%) elderly patients with a mean age of 81 ± 5 years. In-hospital survival was lower in elderly patients compared with younger patients with rates of 33% versus 57% ( p < 0.001). A CPC of 1 was present in 73% of the elderly patients versus 86% of the younger patients ( p = 0.031). In 7.3% of the elderly patients, a CPC >2 was observed versus 2.5% of their younger counterparts ( p = 0.103). Elderly patients had a median survival of 6.5 [95% confidence interval (CI) 2.0-7.9] years compared with 7.7 (95% CI 7.5-7.9) years of the general population ( p = 0.019). CONCLUSIONS:: The survival rate after OHCA in elderly patients is approximately half that of younger patients. Elderly patients who survive to discharge frequently have favorable neurological outcomes and a long-term survival that approximates that of the general population.
Impact of preoperative elevated serum creatinine on long-term outcome of patients undergoing aortic repair with Stanford A dissection: a retrospective matched pair analysis.
Eghbalzadeh K, Sabashnikov A, Weber C … +13 more , Zeriouh M, Djordjevic I, Merkle J, Shostak O, Saenko S, Majd P, Liakopoulos O, Rahmanian PB, Madershahian N, Choi YH, Kuhn-Régnier F, Wippermann J, Wahlers T
Ther Adv Cardiovasc Dis · 2018 Nov · PMID 30227769 · Full text
BACKGROUND: The aim of the present study was to determine whether raised preoperative serum creatinine affected the long-term outcome in patients undergoing surgical aortic repair for Stanford A acute aortic dissection (...
BACKGROUND: The aim of the present study was to determine whether raised preoperative serum creatinine affected the long-term outcome in patients undergoing surgical aortic repair for Stanford A acute aortic dissection (AAD). METHODS: A total of 240 patients diagnosed with Stanford A AAD underwent surgical repair from January 2006 to April 2015. A propensity score matching was applied, resulting in 73 pairs consisting of one group with normal and one group with preoperative elevated creatinine levels. The cohorts were well balanced for baseline and preoperative clinical characteristics. Both groups were compared regarding their early postoperative variables, as well as estimated survival with up to 9-year follow up. Also, the impact of acute postoperative kidney injury and its severity on long-term survival was analyzed. RESULTS: The proportion of patients suffering Stanford A AAD with raised creatinine levels was 31.3% ( n = 75). After propensity matching, there were no statistically significant differences regarding demographics, comorbidities, preoperative baseline and clinical characteristics. Postoperatively matched patients with elevated creatinine had longer intensive care unit ( p < 0.001) and total hospital stay ( p = 0.002), prolonged intubation times ( p = 0.014), higher need for hemofiltration ( p < 0.001), higher incidence of temporary neurological disorders ( p = 0.16), infection ( p = 0.005), and trend toward higher incidence of sepsis ( p = 0.097). However, there were no significant differences regarding 30-day mortality (20.5% versus 20.5%, p = 1.000) and long-term overall survival. Further, neither the incidence nor the different stages of acute kidney injury according to the Acute Kidney Injury Network showed any statistically significant differences in terms of long-term survival for both groups [log rank p = 0.636, Breslow (generalized Wilcoxon) p = 0.470, Tarone-Ware p = 0.558]. CONCLUSIONS: Patients with elevated creatinine levels undergoing surgical repair for Stanford A AAD demonstrate higher rate of early postoperative complications. However, 30-day mortality and long-term survival in this patient cohort is not significantly impaired.
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