Asymptomatic organ damage due to progressive kidney damage, cardiac hypertrophy and remodeling put hypertensive patients at high risk for developing heart and renal failure, myocardial infarction and stroke. Current a...Asymptomatic organ damage due to progressive kidney damage, cardiac hypertrophy and remodeling put hypertensive patients at high risk for developing heart and renal failure, myocardial infarction and stroke. Current antihypertensive treatment normalizes high blood pressure, partially reverses organ damage, and reduces the incidence of heart and renal failure. Activation of the renin-angiotensin system(RAS) is a primary mechanism of progressive organ damage and, specifically, a major cause of both renal and cardiovascular fibrosis. Currently, inhibition of the RAS system [mainly with angiotensin I converting enzyme inhibitors or angiotensin II(Ang II) receptor antagonists] is the most effective antihypertensive strategy for normalizing blood pressure and preventing target organ damage. However, residual organ damage and consequently high risk for cardiovascular events and renal failure still persist. Accordingly, in hypertension, it is relevant to develop new therapeutic perspectives, beyond reducing blood pressure to further prevent/reduce target organ damage by acting on pathways that trigger and maintain cardiovascular and renal remodeling. We review here relevant novel mechanisms of target organ damage in hypertension, their role and evidence in prevention/regression of cardiovascular remodeling and their possible clinical impact as well. Specifically, we focus on the signaling pathway Rho A/Rho kinase, on the impact of the vasodilatory peptides from the RAS and some insights on the role of estrogens and myocardial chymase in cardiovascular hypertensive remodeling.展开更多
Cardiovascular disease(CVD)is the number one cause of mortality world-wide and places a high medical and socioeconomic burden on developing countries.Our understanding of CVD and its evolution over the last 100 years ...Cardiovascular disease(CVD)is the number one cause of mortality world-wide and places a high medical and socioeconomic burden on developing countries.Our understanding of CVD and its evolution over the last 100 years has altered considerably.Reasons for the increased rate of CVD in the developing world include rapid urbanization and the demographic shift known as the modern epidemiologic transition.The case for intervention is based on both major human and economic impacts of CVD.It has been estimated that cost-effective interventions in developing countries with a high burden of CVD could result in a projected 24 million lives saved.This reduction in CVD mortality could reduce economic costs by$8 billion.Approaches to intervention include:1)cardiovascular health promotion and CVD prevention and 2)action plans advocated by the World Health Organization.展开更多
Ischemia/reperfusion (I/R) injury is an inflammatory condition that is characterized by innate immunity and an adaptive immune response. This review is focused on the acute inflammatory response in I/R injury, and als...Ischemia/reperfusion (I/R) injury is an inflammatory condition that is characterized by innate immunity and an adaptive immune response. This review is focused on the acute inflammatory response in I/R injury, and also the adaptive immunological mechanisms in chronic ischemic disease that lead to increased vulnerability during acute events, in relation to the cell types that have been shown to mediate innate immunity to an adaptive immune response in I/R, specifically myocardial infarction. Novel aspects are also highlighted in respect to the mechanisms within the cardiovascular system and cardiovascular risk factors that may be involved in the inflammatory response accompanying myocardial infarction. Experimental myocardial I/R has suggested that immune cells may mediate reperfusion injury. Specifically, monocytes, macrophages, T-cells, mast cells,platelets and endothelial cells are discussed with reference to the complement cascade, toll-like receptors, cytokines, oxidative stress, renin-angiotensin system, and in reference to the microvascular system in the signaling mechanisms of I/R. Finally, the findings of the data summarized in this review are most important for possible translation into clinical cardiology practice and possible avenues for drug development.展开更多
AIM To investigate if patent foramen ovale(PFO) closure device reduces the risk of recurrent stroke in patients with cryptogenic stroke.METHODS We searched five databases-Pub Med,EMBASE,Cochrane,CINAHL and Web-of-Scie...AIM To investigate if patent foramen ovale(PFO) closure device reduces the risk of recurrent stroke in patients with cryptogenic stroke.METHODS We searched five databases-Pub Med,EMBASE,Cochrane,CINAHL and Web-of-Science and clinicaltrials.gov from January 2000 to September 2017 for randomized trials comparing PFO closure to medical therapy in cryptogenic stroke.Heterogeneity was determined using Cochrane's Q statistics.Random effects model was used.RESULTS Five randomized controlled trials with 3440 patients were included in the analysis.Mean follow-up was 50 ± 20 mo.PFO closure was associated with a 41% reduction in incidence of recurrent strokes when compared to medical therapy alone in patients with cryptogenic stroke [risk ratio(RR): 0.59,95%CI: 0.40-0.87,P = 0.008].Atrial fibrillation was higher with device closure when compared to medical therapy alone(RR: 4.97,95%CI: 2.22-11.11,P < 0.001).There was no difference between the two groups with respect to all-cause mortality,major bleeding or adverse events.CONCLUSION PFO device closure in appropriately selected patients with moderate to severe right-to-left shunt and/or atrial septal aneurysm shows benefit with respect to recurrent strokes,particularly in younger patients.Further studies are essential to evaluate the impact of higher incidence of atrial fibrillation seen with the PFO closure device on long-term mortality and stroke rates.展开更多
Human aging is a global issue with important implications for current and future incidence and prevalence of health conditions and disability. Cardiac arrhythmias, including atrial fibrillation, sudden cardiac death, ...Human aging is a global issue with important implications for current and future incidence and prevalence of health conditions and disability. Cardiac arrhythmias, including atrial fibrillation, sudden cardiac death, and bradycardia requiring pacemaker placement, all increase exponentially after the age of 60. It is important to distinguish between the normal, physiological consequences of aging on cardiac electrophysiology and the abnormal, pathological alterations. The age-related cardiac changes include ventricular hypertrophy, senile amyloidosis, cardiac valvular degenerative changes and annular calcification, fibrous infiltration of the conduction system, and loss of natural pacemaker cells and these changes could have a profound effect on the development of arrhythmias. The age-related cardiac electrophysiological changes include up- and down-regulation of specific ion channel expression and intmcellular Ca2+ overload which promote the development of cardiac arrhythmias. As ion channels are the substrates of antiarrhythmic drugs, it follows that the pharmacokinetics and pharmacodynamics of these drugs will also change with age. Aging alters the absorption, distribution, metabolism, and elimination of antiarrhythmic drugs, so liver and kidney function must be monitored to avoid potential adverse drug effects, and antiarrhythmic dosing may need to be adjusted for age. Elderly patients are also more susceptible to the side effects of many antiarrhytbanics, including bradycardia, orthostatic hypotension, urinary retention, and falls. Moreover, the choice of antiarrhythmic drugs in the elderly patient is frequently complicated by the presence of co-morbid conditions and by polypharmacy, and the astute physician must pay careful attention to potential drug-drug interactions. Finally, it is important to remember that the use of antiarrhythmic drugs in elderly patients must be individualized and tailored to each patient's physiology, disease processes, and medication regimen.展开更多
AIM To perform a systematic-review and meta-analysis to compare outcomes of ivabradine combined with betablocker to beta-blocker alone in heart failure with reduced ejection fraction(HFr EF).METHODS We searched PubM e...AIM To perform a systematic-review and meta-analysis to compare outcomes of ivabradine combined with betablocker to beta-blocker alone in heart failure with reduced ejection fraction(HFr EF).METHODS We searched PubM ed, Cochrane, EMBASE, CINAHL and Web of Science for trials comparing ivabradine + betablocker to beta-blocker alone in HFr EF. We performed a systematic-review and meta-analysis of published literature. Primary end-point was combined end point of cardiac death and hospitalization for heart failure.RESULTS Six studies with 17671 patients were included. Mean follow-up was 8.7 ± 7.9 mo. Combined end-point of heart failure readmission and cardiovascular death was better in ivabradine + beta-blocker group compared to beta-blocker alone(RR: 0.93, 95%CI: 0.79-1.09, P = 0.354). Mean difference(MD) in heart rate was higher in the ivabradine + beta-blocker group(MD: 6.14, 95%CI: 3.80-8.48, P < 0.001). There was no difference in all cause mortality(RR: 0.98, 95%CI: 0.89-1.07, P = 0.609), cardiovascular mortality(RR: 0.99, 95%CI: 0.86-1.15, P = 0.908) or heart failure hospitalization(RR: 0.87, 95%CI: 0.68-1.11, P = 0.271). CONCLUSION From the available clinical trials, ivabradine + betablocker resulted in a significantly greater reduction in HRcoupled with improvement in combined end-point of heart failure readmission and cardiovascular death but with no improvement in all cause or cardiovascular mortality. Given the limited evidence, further randomized controlled trials are essential before widespread clinical application of ivabradine + beta-blocker is advocated for HFrEF.展开更多
AIM To investigate the patient-outcomes of newly developed pressure drop coefficient(CDP) in diagnosing epicardial stenosis(ES) in the presence of concomitant microvascular disease(MVD).METHODS Patients from our clini...AIM To investigate the patient-outcomes of newly developed pressure drop coefficient(CDP) in diagnosing epicardial stenosis(ES) in the presence of concomitant microvascular disease(MVD).METHODS Patients from our clinical trial were divided into two subgroups with:(1) cut-off of coronary flow reserve(CFR) < 2.0;and(2) diabetes.First,correlations were performed for both subgroups between CDP and hyperemic microvascular resistance(HMR),a diagnostic parameter for assessing the severity of MVD.Linear regression analysis was used for these correlations.Further,in each of the subgroups,comparisons were made between fractional flow reserve(FFR) < 0.75 and CDP > 27.9 groups for assessing major adverse cardiac events(MACE:Primary outcome).Comparisons were also made between the survival curves for FFR < 0.75 and CDP > 27.9 groups.Two tailed chi-squared and Fischer's exact tests were performed for comparison of the primary outcomes,and the log-rank test was used to compare the Kaplan-Meier survival curves.P < 0.05 for all tests was considered statistically significant.RESULTS Significant linear correlations were observed between CDP and HMR for both CFR < 2.0(r = 0.58,P < 0.001) and diabetic(r = 0.61,P < 0.001) patients.In the CFR < 2.0 subgroup,the %MACE(primary outcomes) for CDP > 27.9 group(7.7%,2/26) was lower than FFR < 0.75 group(3/14,21.4%);P = 0.21.Similarly,in the diabetic subgroup,the %MACE for CDP > 27.9 group(12.5%,2/16) was lower than FFR < 0.75 group(18.2%,2/11);P = 0.69.Survival analysis for CFR < 2.0 subgroup indicated better event-free survival for CDP > 27.9 group(n = 26) when compared with FFR < 0.75 group(n = 14);P = 0.10.Similarly,for the diabetic subgroup,CDP > 27.9 group(n = 16) showed higher survival times compared to FFR group(n = 11);P = 0.58.CONCLUSION CDP correlated significantly with HMR and resulted in better %MACE as well as survival rates in comparison to FFR.These positive trends demonstrate that CDP could be a potential diagnostic endpoint for delineating MVD with or without ES.展开更多
Aortic stenosis(AS) is a disease that progresses slowly for years without symptoms, so patients need to be carefully managed with appropriate follow up and referred for aortic valve replacement in a timely manner. Dev...Aortic stenosis(AS) is a disease that progresses slowly for years without symptoms, so patients need to be carefully managed with appropriate follow up and referred for aortic valve replacement in a timely manner. Development of symptoms is a clear indication for aortic valve intervention in patients with severe AS. The decision for early surgery in patients with asymptomatic severe AS is more complex. In this review, we discuss how to identify high-risk patients with asymptomatic severe AS who may benefit from early surgery.展开更多
We report three cases of Takotsubo syndrome(TS) with atypical myocardial involvement. All three cases were triggered by physical or mental stress, resulting in transient myocardial compromise. However, the clinical pr...We report three cases of Takotsubo syndrome(TS) with atypical myocardial involvement. All three cases were triggered by physical or mental stress, resulting in transient myocardial compromise. However, the clinical presentation, localization and extent of myocardial damage varied in each case, ranging from low-risk acute chest pain to cardiogenic shock with low ejection fraction and dynamic obstruction of the left ventricular outflow tract. These cases outline the range of possible presentations of this rare entity and illustrate atypical forms of TS.展开更多
Background Corrected QT dispersion (cQTD) has been correlated with non-uniform ventricular repolarisation and increased mortality. In patients with aortic stenosis, cQTD has been shown improved after surgical valve ...Background Corrected QT dispersion (cQTD) has been correlated with non-uniform ventricular repolarisation and increased mortality. In patients with aortic stenosis, cQTD has been shown improved after surgical valve replacement, but the effects of transcatheter aortic valve implantation (TAVI) are unknown. Therefore, we sought to explore the frequency, predictors and prognostic effects of defective cQTD recovery at 6 months after TAVI. Methods A total of 222 patients underwent TAVI with the Medtronic-CoreValve System between November 2005 and January 2012. Patients who were on class Ⅰ or Ⅲ antiarrhythmics or on chronic haemodialysis or who developed atrial fibrillation, a new bundle branch block or became pacemaker dependent after TAVI were excluded. As a result, pre-, post- and follow-up ECG (median: 6 months) analysis was available in 45 eligible patients. Defective cQTD recovery was defined as any progression beyond the baseline cQTD at 6 months. Results In the 45 patients, the mean cQTD was 47 ± 23 ms at baseline, 45 ±17 ms immediately after TAVI and 40 ± 16 ms at 6 months (15% reduction, P = 0.049). Compared to baseline, cQTD at 6 months was improved in 60% of the patients whereas defective cQTD recovery was present in 40%. cQTD increase immediately after TAVI was an independent predictor of defective cQTD recovery at 6 months (per 10 ms increase; OR: 1.89, 95% CI: 1.15-3.12). By univariable analysis, defective cQTD recovery was associated with late mortality (HR: 1.52, 95% CI: 1.05-2.17). Conclusions Despite a gradual reduction ofcQTD after TAVI, 40% of the patients had defective recovery at 6 months which was associated with late mortality. More detailed ECG analysis after TAVI may help to avoid late death.展开更多
1 Introduction Hypertension and cerebrovascular disease incidence and prevalence rise dramatically with age, owing to longer exposure time to age-associated alterations in vascular function and structure and cardiova...1 Introduction Hypertension and cerebrovascular disease incidence and prevalence rise dramatically with age, owing to longer exposure time to age-associated alterations in vascular function and structure and cardiovascular risk factors. This chapter is aimed at connecting age-related alterations in vascular function and structure to the resultant target organ damage, and to raise awareness of unique presentations and treatment strategies for hypertension and stroke in older adults.展开更多
1 Introduction Although older adults are generally among the highest users of cardiovascular medications, they are typically underrepresented or excluded from most efficacy and safety trials. Drug developers are usual...1 Introduction Although older adults are generally among the highest users of cardiovascular medications, they are typically underrepresented or excluded from most efficacy and safety trials. Drug developers are usually reluctant to include many senior adults in randomized controlled clinical trials in part due to their high prevalence of multiple comorbidities, frailty, and polypharmacy; and to age-related pharmacokinetic and pharmacodynamic complexities. Consequently, there is often insufficient high quality evidence-based data to inform pharmacologic management of common cardiovascular conditions on older adults. In the absence of data, clinicians often rely on conceptual principles regarding metabolism and drug-drug interactions to minimize adverse drug events, but this is often not well-substantiated or standardized. A related challenge is poor cardiovascular medication adherence among older adults, and its detrimental impact on their health outcomes. In this brief review we highlight some aspects of these topics.展开更多
Papillary fibroelastomas (PFEs) are benign tumors of the endocardium that most frequently affect cardiac valves and typically present with embolic symptoms such as stroke or transient ischemic attack (TIA). Surgical e...Papillary fibroelastomas (PFEs) are benign tumors of the endocardium that most frequently affect cardiac valves and typically present with embolic symptoms such as stroke or transient ischemic attack (TIA). Surgical excision is usually recommended for left-sided tumors and is associated with excellent long-term outcomes. The use of a robot-assisted, minimally invasive surgical approach for management of mitral valve disease is growing, and has been associated with shorter hospital stays and improved early quality of life. Three-dimensional (3D) transesophageal echocardiography (TEE) offers several advantages in the assessment of mitral valve disease and cardiac tumors, including the ability to precisely locate the site of attachment of the mass and the spatial relationships to surrounding structures. These factors are particularly important when planning a surgical approach. We report two cases of mitral valve PFEs which were successfully removed using a robot-assisted, minimally invasive surgical approach with 3D TEE imaging. This approach to treatment of PFEs is an attractive alternative to the traditional approach involving median sternotomy.展开更多
Background Co-existence of obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD) is referred to as overlap syndrome. Overlap patients have greater degree of hypoxia and pulmonary hypertension ...Background Co-existence of obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD) is referred to as overlap syndrome. Overlap patients have greater degree of hypoxia and pulmonary hypertension than patients with OSA or COPD alone. Studies showed that elderly patients with OSA alone do not have increased risk of atrial fibrillation (AF) but it is not known if overlap patients have higher risk of AF. Objective To determine whether elderly patients with overlap syndrome have an increased risk of AF. Methods In this single center, community-based retrospective cohort analysis, data were collected on 2,873 patients > 65 years of age without AF, presenting in the year 2006. Patients were divided into OSA group (n = 60), COPD group (n = 416), overlap syndrome group (n = 28) and group with no OSA or COPD(n = 2369). The primary endpoint was incidence of new-onset AF over the following two years. Logistic regression was performed to adjust for heart failure (HF), coronary artery disease, hypertension (HTN), cerebrovascular disease, cardiac valve disorders, diabetes mellitus, hyperlipidemia, chronic kidney disease (CKD) and obesity. Results The incidence of AF was 10% in COPD group, 6% in OSA group and 21% in overlap syndrome group (P < 0.05). After adjusting for age, sex, HF, CKD, and HTN, patientswith overlap syndrome demonstrated a significant association with new-onset AF (OR = 3.66, P = 0.007). HF, CKD and HTNwere also significantly associated with new-onset AF (P < 0.05). Conclusion Among elderly patients, the presence of overlap syndrome is associatedwith a marked increase in risk of new-onset AF as compared to the presence of OSA or COPDalone.展开更多
Benign prostatic hyperplasia(BPH)is a pathologic condition of the prostate described as a substantial increase in its number of epithelial and stromal cells.BPH may significantly reduce the quality of life due to the ...Benign prostatic hyperplasia(BPH)is a pathologic condition of the prostate described as a substantial increase in its number of epithelial and stromal cells.BPH may significantly reduce the quality of life due to the initiation of bladder outlet obstruction and lower urinary tract syndromes.Current medical therapies mostly consist of inhibitors of 5α-reductase orα1-adrenergic blockers;their efficacy is often insufficient.Antagonistic analogs of neuropeptide hormones are novel candidates for the management of BPH.At first,antagonists of luteinizing hormone-releasing hormone(LHRH)have been introduced to the therapy aimed to reduce serum testosterone levels.However,they have also been found to produce an inhibitory activity on local LHRH receptors in the prostate as well as impotence and other related side effects.Since then,several preclinical and clinical studies reported the favorable effects of LHRH antagonists in BPH.In contrast,antagonists of growth hormone-releasing hormone(GHRH)and gastrin-releasing peptide(GRP)have been tested only in preclinical settings and produce significant reduction in prostate size in experimental models of BPH.They act at least in part,by blocking the action of respective ligands produced locally on prostates through their respective receptors in the prostate,and by inhibition of autocrine insulin-like growth factors-Ⅰ/Ⅱand epidermal growth factor production.GHRH and LHRH antagonists were also tested in combination resulting in a cumulative effect that was greater than that of each alone.This article will review the numerous studies that demonstrate the beneficial effects of antagonistic analogs of LHRH,GHRH and GRP in BPH,as well as suggesting a potential role for somatostatin analogs in experimental therapies.展开更多
Background Pulmonary veins (PV) and the atria undergo electrical and structural remodeling in atrial fibrillation (AF). This study aimed to determine PV and left atrial (LA) reverse remodeling after catheter abl...Background Pulmonary veins (PV) and the atria undergo electrical and structural remodeling in atrial fibrillation (AF). This study aimed to determine PV and left atrial (LA) reverse remodeling after catheter ablation for AF assessed by chest computed tomography (CT). Methods PV electrophysiologic studies and catheter ablation were performed in 63 patients (68% male; mean ± SD age: 56 ± 10 years) with symptomatic AF (49% paroxysmal, 51% persistent). Chest CT was performed before and 3 months after catheter ablation. Results At baseline, patients with persistent AF had a greater LA volume (91 ±29 cm3 vs. 66 ± 27 cm3; P = 0.003) and mean PV ostial area (241 + 43 mm2 vs. 212 ± 47 mm2; P = 0.03) than patients with paroxysmal AF. There was no significant correlation between the effective refractory period and the area of the left superior PV ostium. At 3 months of follow-up after ablation, 48 patients (76%) were AF free on or off antiarrhythmic drugs. There was a significant reduction in LA volume (77 ±31 cm3 to 70 ± 28 cm3; P 〈 0.001) and mean PV ostial area (224 ± 48 mm2 to 182 ± 43 mm2; P 〈 0.001). Patients with persistent AF had more reduction in LA volume (11.8 ± 12.8 cm3 vs. 4.0 ± 11.2 cm3; P = 0.04) and PV ostial area (62 mm2 vs. 34 mm2; P = 0.04) than those who have paroxysmal AF. The reduction of the averaged PV ostial area was significantly correlated with the reduction of LA volume (r = 0.38, P = 0.03). Conclusions Catheter ablation of AF improves structural remodeling ofPV ostia and left atrium. This finding is more apparent in patients with persistent AF treated by catheter ablation.展开更多
BACKGROUND Treatment of congenitally corrected transposition of great arteries(cc-TGA)with anatomic repair strategy has been considered superior due to restoration of the morphologic left ventricle in the systemic cir...BACKGROUND Treatment of congenitally corrected transposition of great arteries(cc-TGA)with anatomic repair strategy has been considered superior due to restoration of the morphologic left ventricle in the systemic circulation.However,data on long term outcomes are limited to single center reports and include small sample sizes.AIM To perform a systematic review and meta-analysis for observational studies reporting outcomes on anatomic repair for cc-TGA.METHODS MEDLINE and Scopus databases were queried using predefined criteria for reports published till December 31,2017.Studies reporting anatomic repair of minimum 5 cc-TGA patients with at least a 2 year follow up were included.Metaanalysis was performed using Comprehensive meta-analysis v3.0 software.RESULTS Eight hundred and ninety-five patients underwent anatomic repair with a pooled follow-up of 5457.2 patient-years(PY).Pooled estimate for operative mortality was 8.3%[95%confidence interval(CI):6.0%-11.4%].0.2%(CI:0.1%-0.4%)patients required mechanical circulatory support postoperatively and 1.7%(CI:1.1%-2.4%)developed post-operative atrioventricular block requiring a pacemaker.Patients surviving initial surgery had a transplant free survival of 92.5%(CI:89.5%-95.4%)per 100 PY and a low rate of need for pacemaker(0.3/100 PY;CI:0.1-0.4).84.7%patients(CI:79.6%-89.9%)were found to be in New York Heart Association(NYHA)functional class I or II after 100 PY follow up.Total re-intervention rate was 5.3 per 100 PY(CI:3.8-6.8).CONCLUSION Operative mortality with anatomic repair strategy for cc-TGA is high.Despite that,transplant free survival after anatomic repair for cc-TGA patients is highly favorable.Majority of patients maintain NYHA I/II functional class.However,monitoring for burden of re-interventions specific for operation type is very essential.展开更多
BACKGROUND The risk of critical limb ischemia(CLI)which causes ischemic pain or ischemic loss in the arteries of the lower extremities in long-term uterine cancer(UC)survivors remains unclear,especially in Asian patie...BACKGROUND The risk of critical limb ischemia(CLI)which causes ischemic pain or ischemic loss in the arteries of the lower extremities in long-term uterine cancer(UC)survivors remains unclear,especially in Asian patients,who are younger at the diagnosis of UC than their Western counterparts.AIM To conduct a nationwide population-based study to assess the risk of CLI in UC long-term survivors.METHODS UC survivors,defined as those who survived for longer than 5 years after the diagnosis,were identified and matched at a 1:4 ratio with normal controls.Stratified Cox models were used to assess the risk of CLI.RESULTS From 2000 to 2005,1889 UC survivors who received surgery alone or surgery combined with radiotherapy(RT)were classified into younger(onset age<50 years,n=894)and older(onset age≥50 years,n=995)groups.While compared with normal controls,the younger patients with diabetes,hypertension,and receiving hormone replacement therapy(HRT)were more likely to develop CLI.In contrast,the risk of CLI was associated with adjuvant RT,obesity,hypertension,and HRT in the older group.Among the UC survivors,those who were diagnosed at an advanced age(>65 years,aHR=2.48,P=0.011),had hypertension(aHR=2.18,P=0.008)or received HRT(aHR=3.52,P=0.020)were at a higher risk of CLI.CONCLUSION In this nationwide study,we found that the risk factors associated with CLI were similar in both cohorts except for adjuvant RT that was negligible in the younger group,but positive in the older group.Among the survivors,hypertension,advanced age,and HRT were more hazardous than RT.Secondary prevention should include CLI as a late complication in UC survivorship programs.展开更多
基金Supported by Comisión Nacional de Investigación Científicay Tecnológica(CONICYT,Chile)grants FONDECYT 1121060(to JEJ and MPO),FONDEF D11I1122(to MPO and JEJ)and FONDAP 15130011(to MPO)
文摘Asymptomatic organ damage due to progressive kidney damage, cardiac hypertrophy and remodeling put hypertensive patients at high risk for developing heart and renal failure, myocardial infarction and stroke. Current antihypertensive treatment normalizes high blood pressure, partially reverses organ damage, and reduces the incidence of heart and renal failure. Activation of the renin-angiotensin system(RAS) is a primary mechanism of progressive organ damage and, specifically, a major cause of both renal and cardiovascular fibrosis. Currently, inhibition of the RAS system [mainly with angiotensin I converting enzyme inhibitors or angiotensin II(Ang II) receptor antagonists] is the most effective antihypertensive strategy for normalizing blood pressure and preventing target organ damage. However, residual organ damage and consequently high risk for cardiovascular events and renal failure still persist. Accordingly, in hypertension, it is relevant to develop new therapeutic perspectives, beyond reducing blood pressure to further prevent/reduce target organ damage by acting on pathways that trigger and maintain cardiovascular and renal remodeling. We review here relevant novel mechanisms of target organ damage in hypertension, their role and evidence in prevention/regression of cardiovascular remodeling and their possible clinical impact as well. Specifically, we focus on the signaling pathway Rho A/Rho kinase, on the impact of the vasodilatory peptides from the RAS and some insights on the role of estrogens and myocardial chymase in cardiovascular hypertensive remodeling.
文摘Cardiovascular disease(CVD)is the number one cause of mortality world-wide and places a high medical and socioeconomic burden on developing countries.Our understanding of CVD and its evolution over the last 100 years has altered considerably.Reasons for the increased rate of CVD in the developing world include rapid urbanization and the demographic shift known as the modern epidemiologic transition.The case for intervention is based on both major human and economic impacts of CVD.It has been estimated that cost-effective interventions in developing countries with a high burden of CVD could result in a projected 24 million lives saved.This reduction in CVD mortality could reduce economic costs by$8 billion.Approaches to intervention include:1)cardiovascular health promotion and CVD prevention and 2)action plans advocated by the World Health Organization.
基金Supported by Grants from American Heart Association Post-doctoral Fellowship No. 10POST3870022 to Dr. Zuidema MYAmerican Heart Association SDG No. 110350047ANIHgrants No. RO1-HL077566 and RO1-HL085119 to Zhang C
文摘Ischemia/reperfusion (I/R) injury is an inflammatory condition that is characterized by innate immunity and an adaptive immune response. This review is focused on the acute inflammatory response in I/R injury, and also the adaptive immunological mechanisms in chronic ischemic disease that lead to increased vulnerability during acute events, in relation to the cell types that have been shown to mediate innate immunity to an adaptive immune response in I/R, specifically myocardial infarction. Novel aspects are also highlighted in respect to the mechanisms within the cardiovascular system and cardiovascular risk factors that may be involved in the inflammatory response accompanying myocardial infarction. Experimental myocardial I/R has suggested that immune cells may mediate reperfusion injury. Specifically, monocytes, macrophages, T-cells, mast cells,platelets and endothelial cells are discussed with reference to the complement cascade, toll-like receptors, cytokines, oxidative stress, renin-angiotensin system, and in reference to the microvascular system in the signaling mechanisms of I/R. Finally, the findings of the data summarized in this review are most important for possible translation into clinical cardiology practice and possible avenues for drug development.
文摘AIM To investigate if patent foramen ovale(PFO) closure device reduces the risk of recurrent stroke in patients with cryptogenic stroke.METHODS We searched five databases-Pub Med,EMBASE,Cochrane,CINAHL and Web-of-Science and clinicaltrials.gov from January 2000 to September 2017 for randomized trials comparing PFO closure to medical therapy in cryptogenic stroke.Heterogeneity was determined using Cochrane's Q statistics.Random effects model was used.RESULTS Five randomized controlled trials with 3440 patients were included in the analysis.Mean follow-up was 50 ± 20 mo.PFO closure was associated with a 41% reduction in incidence of recurrent strokes when compared to medical therapy alone in patients with cryptogenic stroke [risk ratio(RR): 0.59,95%CI: 0.40-0.87,P = 0.008].Atrial fibrillation was higher with device closure when compared to medical therapy alone(RR: 4.97,95%CI: 2.22-11.11,P < 0.001).There was no difference between the two groups with respect to all-cause mortality,major bleeding or adverse events.CONCLUSION PFO device closure in appropriately selected patients with moderate to severe right-to-left shunt and/or atrial septal aneurysm shows benefit with respect to recurrent strokes,particularly in younger patients.Further studies are essential to evaluate the impact of higher incidence of atrial fibrillation seen with the PFO closure device on long-term mortality and stroke rates.
文摘Human aging is a global issue with important implications for current and future incidence and prevalence of health conditions and disability. Cardiac arrhythmias, including atrial fibrillation, sudden cardiac death, and bradycardia requiring pacemaker placement, all increase exponentially after the age of 60. It is important to distinguish between the normal, physiological consequences of aging on cardiac electrophysiology and the abnormal, pathological alterations. The age-related cardiac changes include ventricular hypertrophy, senile amyloidosis, cardiac valvular degenerative changes and annular calcification, fibrous infiltration of the conduction system, and loss of natural pacemaker cells and these changes could have a profound effect on the development of arrhythmias. The age-related cardiac electrophysiological changes include up- and down-regulation of specific ion channel expression and intmcellular Ca2+ overload which promote the development of cardiac arrhythmias. As ion channels are the substrates of antiarrhythmic drugs, it follows that the pharmacokinetics and pharmacodynamics of these drugs will also change with age. Aging alters the absorption, distribution, metabolism, and elimination of antiarrhythmic drugs, so liver and kidney function must be monitored to avoid potential adverse drug effects, and antiarrhythmic dosing may need to be adjusted for age. Elderly patients are also more susceptible to the side effects of many antiarrhytbanics, including bradycardia, orthostatic hypotension, urinary retention, and falls. Moreover, the choice of antiarrhythmic drugs in the elderly patient is frequently complicated by the presence of co-morbid conditions and by polypharmacy, and the astute physician must pay careful attention to potential drug-drug interactions. Finally, it is important to remember that the use of antiarrhythmic drugs in elderly patients must be individualized and tailored to each patient's physiology, disease processes, and medication regimen.
文摘AIM To perform a systematic-review and meta-analysis to compare outcomes of ivabradine combined with betablocker to beta-blocker alone in heart failure with reduced ejection fraction(HFr EF).METHODS We searched PubM ed, Cochrane, EMBASE, CINAHL and Web of Science for trials comparing ivabradine + betablocker to beta-blocker alone in HFr EF. We performed a systematic-review and meta-analysis of published literature. Primary end-point was combined end point of cardiac death and hospitalization for heart failure.RESULTS Six studies with 17671 patients were included. Mean follow-up was 8.7 ± 7.9 mo. Combined end-point of heart failure readmission and cardiovascular death was better in ivabradine + beta-blocker group compared to beta-blocker alone(RR: 0.93, 95%CI: 0.79-1.09, P = 0.354). Mean difference(MD) in heart rate was higher in the ivabradine + beta-blocker group(MD: 6.14, 95%CI: 3.80-8.48, P < 0.001). There was no difference in all cause mortality(RR: 0.98, 95%CI: 0.89-1.07, P = 0.609), cardiovascular mortality(RR: 0.99, 95%CI: 0.86-1.15, P = 0.908) or heart failure hospitalization(RR: 0.87, 95%CI: 0.68-1.11, P = 0.271). CONCLUSION From the available clinical trials, ivabradine + betablocker resulted in a significantly greater reduction in HRcoupled with improvement in combined end-point of heart failure readmission and cardiovascular death but with no improvement in all cause or cardiovascular mortality. Given the limited evidence, further randomized controlled trials are essential before widespread clinical application of ivabradine + beta-blocker is advocated for HFrEF.
基金Supported by VA Merit Review Grant,Department of Veteran Affairs(PI:Dr.Rupak K Banerjee)No.I01CX000342-01
文摘AIM To investigate the patient-outcomes of newly developed pressure drop coefficient(CDP) in diagnosing epicardial stenosis(ES) in the presence of concomitant microvascular disease(MVD).METHODS Patients from our clinical trial were divided into two subgroups with:(1) cut-off of coronary flow reserve(CFR) < 2.0;and(2) diabetes.First,correlations were performed for both subgroups between CDP and hyperemic microvascular resistance(HMR),a diagnostic parameter for assessing the severity of MVD.Linear regression analysis was used for these correlations.Further,in each of the subgroups,comparisons were made between fractional flow reserve(FFR) < 0.75 and CDP > 27.9 groups for assessing major adverse cardiac events(MACE:Primary outcome).Comparisons were also made between the survival curves for FFR < 0.75 and CDP > 27.9 groups.Two tailed chi-squared and Fischer's exact tests were performed for comparison of the primary outcomes,and the log-rank test was used to compare the Kaplan-Meier survival curves.P < 0.05 for all tests was considered statistically significant.RESULTS Significant linear correlations were observed between CDP and HMR for both CFR < 2.0(r = 0.58,P < 0.001) and diabetic(r = 0.61,P < 0.001) patients.In the CFR < 2.0 subgroup,the %MACE(primary outcomes) for CDP > 27.9 group(7.7%,2/26) was lower than FFR < 0.75 group(3/14,21.4%);P = 0.21.Similarly,in the diabetic subgroup,the %MACE for CDP > 27.9 group(12.5%,2/16) was lower than FFR < 0.75 group(18.2%,2/11);P = 0.69.Survival analysis for CFR < 2.0 subgroup indicated better event-free survival for CDP > 27.9 group(n = 26) when compared with FFR < 0.75 group(n = 14);P = 0.10.Similarly,for the diabetic subgroup,CDP > 27.9 group(n = 16) showed higher survival times compared to FFR group(n = 11);P = 0.58.CONCLUSION CDP correlated significantly with HMR and resulted in better %MACE as well as survival rates in comparison to FFR.These positive trends demonstrate that CDP could be a potential diagnostic endpoint for delineating MVD with or without ES.
文摘Aortic stenosis(AS) is a disease that progresses slowly for years without symptoms, so patients need to be carefully managed with appropriate follow up and referred for aortic valve replacement in a timely manner. Development of symptoms is a clear indication for aortic valve intervention in patients with severe AS. The decision for early surgery in patients with asymptomatic severe AS is more complex. In this review, we discuss how to identify high-risk patients with asymptomatic severe AS who may benefit from early surgery.
基金Supported by a CONICYT research Grant(FONDECYT Iniciación 11170205)for Dr Gonzalo Martínez
文摘We report three cases of Takotsubo syndrome(TS) with atypical myocardial involvement. All three cases were triggered by physical or mental stress, resulting in transient myocardial compromise. However, the clinical presentation, localization and extent of myocardial damage varied in each case, ranging from low-risk acute chest pain to cardiogenic shock with low ejection fraction and dynamic obstruction of the left ventricular outflow tract. These cases outline the range of possible presentations of this rare entity and illustrate atypical forms of TS.
文摘Background Corrected QT dispersion (cQTD) has been correlated with non-uniform ventricular repolarisation and increased mortality. In patients with aortic stenosis, cQTD has been shown improved after surgical valve replacement, but the effects of transcatheter aortic valve implantation (TAVI) are unknown. Therefore, we sought to explore the frequency, predictors and prognostic effects of defective cQTD recovery at 6 months after TAVI. Methods A total of 222 patients underwent TAVI with the Medtronic-CoreValve System between November 2005 and January 2012. Patients who were on class Ⅰ or Ⅲ antiarrhythmics or on chronic haemodialysis or who developed atrial fibrillation, a new bundle branch block or became pacemaker dependent after TAVI were excluded. As a result, pre-, post- and follow-up ECG (median: 6 months) analysis was available in 45 eligible patients. Defective cQTD recovery was defined as any progression beyond the baseline cQTD at 6 months. Results In the 45 patients, the mean cQTD was 47 ± 23 ms at baseline, 45 ±17 ms immediately after TAVI and 40 ± 16 ms at 6 months (15% reduction, P = 0.049). Compared to baseline, cQTD at 6 months was improved in 60% of the patients whereas defective cQTD recovery was present in 40%. cQTD increase immediately after TAVI was an independent predictor of defective cQTD recovery at 6 months (per 10 ms increase; OR: 1.89, 95% CI: 1.15-3.12). By univariable analysis, defective cQTD recovery was associated with late mortality (HR: 1.52, 95% CI: 1.05-2.17). Conclusions Despite a gradual reduction ofcQTD after TAVI, 40% of the patients had defective recovery at 6 months which was associated with late mortality. More detailed ECG analysis after TAVI may help to avoid late death.
文摘1 Introduction Hypertension and cerebrovascular disease incidence and prevalence rise dramatically with age, owing to longer exposure time to age-associated alterations in vascular function and structure and cardiovascular risk factors. This chapter is aimed at connecting age-related alterations in vascular function and structure to the resultant target organ damage, and to raise awareness of unique presentations and treatment strategies for hypertension and stroke in older adults.
文摘1 Introduction Although older adults are generally among the highest users of cardiovascular medications, they are typically underrepresented or excluded from most efficacy and safety trials. Drug developers are usually reluctant to include many senior adults in randomized controlled clinical trials in part due to their high prevalence of multiple comorbidities, frailty, and polypharmacy; and to age-related pharmacokinetic and pharmacodynamic complexities. Consequently, there is often insufficient high quality evidence-based data to inform pharmacologic management of common cardiovascular conditions on older adults. In the absence of data, clinicians often rely on conceptual principles regarding metabolism and drug-drug interactions to minimize adverse drug events, but this is often not well-substantiated or standardized. A related challenge is poor cardiovascular medication adherence among older adults, and its detrimental impact on their health outcomes. In this brief review we highlight some aspects of these topics.
文摘Papillary fibroelastomas (PFEs) are benign tumors of the endocardium that most frequently affect cardiac valves and typically present with embolic symptoms such as stroke or transient ischemic attack (TIA). Surgical excision is usually recommended for left-sided tumors and is associated with excellent long-term outcomes. The use of a robot-assisted, minimally invasive surgical approach for management of mitral valve disease is growing, and has been associated with shorter hospital stays and improved early quality of life. Three-dimensional (3D) transesophageal echocardiography (TEE) offers several advantages in the assessment of mitral valve disease and cardiac tumors, including the ability to precisely locate the site of attachment of the mass and the spatial relationships to surrounding structures. These factors are particularly important when planning a surgical approach. We report two cases of mitral valve PFEs which were successfully removed using a robot-assisted, minimally invasive surgical approach with 3D TEE imaging. This approach to treatment of PFEs is an attractive alternative to the traditional approach involving median sternotomy.
文摘Background Co-existence of obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD) is referred to as overlap syndrome. Overlap patients have greater degree of hypoxia and pulmonary hypertension than patients with OSA or COPD alone. Studies showed that elderly patients with OSA alone do not have increased risk of atrial fibrillation (AF) but it is not known if overlap patients have higher risk of AF. Objective To determine whether elderly patients with overlap syndrome have an increased risk of AF. Methods In this single center, community-based retrospective cohort analysis, data were collected on 2,873 patients > 65 years of age without AF, presenting in the year 2006. Patients were divided into OSA group (n = 60), COPD group (n = 416), overlap syndrome group (n = 28) and group with no OSA or COPD(n = 2369). The primary endpoint was incidence of new-onset AF over the following two years. Logistic regression was performed to adjust for heart failure (HF), coronary artery disease, hypertension (HTN), cerebrovascular disease, cardiac valve disorders, diabetes mellitus, hyperlipidemia, chronic kidney disease (CKD) and obesity. Results The incidence of AF was 10% in COPD group, 6% in OSA group and 21% in overlap syndrome group (P < 0.05). After adjusting for age, sex, HF, CKD, and HTN, patientswith overlap syndrome demonstrated a significant association with new-onset AF (OR = 3.66, P = 0.007). HF, CKD and HTNwere also significantly associated with new-onset AF (P < 0.05). Conclusion Among elderly patients, the presence of overlap syndrome is associatedwith a marked increase in risk of new-onset AF as compared to the presence of OSA or COPDalone.
基金Supported by The Medical Research Service of the Veterans Affairs Department,Departments of Pathology and Medicine,Division of Hematology/Oncology,Sylvester Comprehensive Cancer Center,University of Miami,Miller School of Medicine,the South Florida Veterans Affairs Foundation for Research and Education(all to Schally AV)the L Austin Weeks Endowment for Urologic Research(to Block NL)+2 种基金in part by a grant from the Urology Care Foundation Research Scholars Program and the American Urological Association(AUA)Southeastern Section(to Rick FG)by a stipend program of the Department of Medicine,Dresdenby the Helmholtz Alliance ICEMED(Imaging and Curing Environmental Metabolic Diseases)through the Initiative and Networking Fund of the Helmholtz Association(to Popovics P)
文摘Benign prostatic hyperplasia(BPH)is a pathologic condition of the prostate described as a substantial increase in its number of epithelial and stromal cells.BPH may significantly reduce the quality of life due to the initiation of bladder outlet obstruction and lower urinary tract syndromes.Current medical therapies mostly consist of inhibitors of 5α-reductase orα1-adrenergic blockers;their efficacy is often insufficient.Antagonistic analogs of neuropeptide hormones are novel candidates for the management of BPH.At first,antagonists of luteinizing hormone-releasing hormone(LHRH)have been introduced to the therapy aimed to reduce serum testosterone levels.However,they have also been found to produce an inhibitory activity on local LHRH receptors in the prostate as well as impotence and other related side effects.Since then,several preclinical and clinical studies reported the favorable effects of LHRH antagonists in BPH.In contrast,antagonists of growth hormone-releasing hormone(GHRH)and gastrin-releasing peptide(GRP)have been tested only in preclinical settings and produce significant reduction in prostate size in experimental models of BPH.They act at least in part,by blocking the action of respective ligands produced locally on prostates through their respective receptors in the prostate,and by inhibition of autocrine insulin-like growth factors-Ⅰ/Ⅱand epidermal growth factor production.GHRH and LHRH antagonists were also tested in combination resulting in a cumulative effect that was greater than that of each alone.This article will review the numerous studies that demonstrate the beneficial effects of antagonistic analogs of LHRH,GHRH and GRP in BPH,as well as suggesting a potential role for somatostatin analogs in experimental therapies.
文摘Background Pulmonary veins (PV) and the atria undergo electrical and structural remodeling in atrial fibrillation (AF). This study aimed to determine PV and left atrial (LA) reverse remodeling after catheter ablation for AF assessed by chest computed tomography (CT). Methods PV electrophysiologic studies and catheter ablation were performed in 63 patients (68% male; mean ± SD age: 56 ± 10 years) with symptomatic AF (49% paroxysmal, 51% persistent). Chest CT was performed before and 3 months after catheter ablation. Results At baseline, patients with persistent AF had a greater LA volume (91 ±29 cm3 vs. 66 ± 27 cm3; P = 0.003) and mean PV ostial area (241 + 43 mm2 vs. 212 ± 47 mm2; P = 0.03) than patients with paroxysmal AF. There was no significant correlation between the effective refractory period and the area of the left superior PV ostium. At 3 months of follow-up after ablation, 48 patients (76%) were AF free on or off antiarrhythmic drugs. There was a significant reduction in LA volume (77 ±31 cm3 to 70 ± 28 cm3; P 〈 0.001) and mean PV ostial area (224 ± 48 mm2 to 182 ± 43 mm2; P 〈 0.001). Patients with persistent AF had more reduction in LA volume (11.8 ± 12.8 cm3 vs. 4.0 ± 11.2 cm3; P = 0.04) and PV ostial area (62 mm2 vs. 34 mm2; P = 0.04) than those who have paroxysmal AF. The reduction of the averaged PV ostial area was significantly correlated with the reduction of LA volume (r = 0.38, P = 0.03). Conclusions Catheter ablation of AF improves structural remodeling ofPV ostia and left atrium. This finding is more apparent in patients with persistent AF treated by catheter ablation.
文摘BACKGROUND Treatment of congenitally corrected transposition of great arteries(cc-TGA)with anatomic repair strategy has been considered superior due to restoration of the morphologic left ventricle in the systemic circulation.However,data on long term outcomes are limited to single center reports and include small sample sizes.AIM To perform a systematic review and meta-analysis for observational studies reporting outcomes on anatomic repair for cc-TGA.METHODS MEDLINE and Scopus databases were queried using predefined criteria for reports published till December 31,2017.Studies reporting anatomic repair of minimum 5 cc-TGA patients with at least a 2 year follow up were included.Metaanalysis was performed using Comprehensive meta-analysis v3.0 software.RESULTS Eight hundred and ninety-five patients underwent anatomic repair with a pooled follow-up of 5457.2 patient-years(PY).Pooled estimate for operative mortality was 8.3%[95%confidence interval(CI):6.0%-11.4%].0.2%(CI:0.1%-0.4%)patients required mechanical circulatory support postoperatively and 1.7%(CI:1.1%-2.4%)developed post-operative atrioventricular block requiring a pacemaker.Patients surviving initial surgery had a transplant free survival of 92.5%(CI:89.5%-95.4%)per 100 PY and a low rate of need for pacemaker(0.3/100 PY;CI:0.1-0.4).84.7%patients(CI:79.6%-89.9%)were found to be in New York Heart Association(NYHA)functional class I or II after 100 PY follow up.Total re-intervention rate was 5.3 per 100 PY(CI:3.8-6.8).CONCLUSION Operative mortality with anatomic repair strategy for cc-TGA is high.Despite that,transplant free survival after anatomic repair for cc-TGA patients is highly favorable.Majority of patients maintain NYHA I/II functional class.However,monitoring for burden of re-interventions specific for operation type is very essential.
基金Supported by the Chang Gung Medical Foundation,Taiwan,No.CMRPD1J0101-0102。
文摘BACKGROUND The risk of critical limb ischemia(CLI)which causes ischemic pain or ischemic loss in the arteries of the lower extremities in long-term uterine cancer(UC)survivors remains unclear,especially in Asian patients,who are younger at the diagnosis of UC than their Western counterparts.AIM To conduct a nationwide population-based study to assess the risk of CLI in UC long-term survivors.METHODS UC survivors,defined as those who survived for longer than 5 years after the diagnosis,were identified and matched at a 1:4 ratio with normal controls.Stratified Cox models were used to assess the risk of CLI.RESULTS From 2000 to 2005,1889 UC survivors who received surgery alone or surgery combined with radiotherapy(RT)were classified into younger(onset age<50 years,n=894)and older(onset age≥50 years,n=995)groups.While compared with normal controls,the younger patients with diabetes,hypertension,and receiving hormone replacement therapy(HRT)were more likely to develop CLI.In contrast,the risk of CLI was associated with adjuvant RT,obesity,hypertension,and HRT in the older group.Among the UC survivors,those who were diagnosed at an advanced age(>65 years,aHR=2.48,P=0.011),had hypertension(aHR=2.18,P=0.008)or received HRT(aHR=3.52,P=0.020)were at a higher risk of CLI.CONCLUSION In this nationwide study,we found that the risk factors associated with CLI were similar in both cohorts except for adjuvant RT that was negligible in the younger group,but positive in the older group.Among the survivors,hypertension,advanced age,and HRT were more hazardous than RT.Secondary prevention should include CLI as a late complication in UC survivorship programs.