The role of assessment of myocardial viability in identifying patients with ischemic cardiomyopathy who might benefit from surgical revascularization remains controversial. Furthermore, although ...improvement in left ventricular function is one of the goals of revascularization, its relationship to subsequent outcomes is unclear.
Among 601 patients who had coronary artery disease that was amenable to coronary-artery bypass grafting (CABG) and who had a left ventricular ejection fraction of 35% or lower, we prospectively assessed myocardial viability using single-photon-emission computed tomography, dobutamine echocardiography, or both. Patients were randomly assigned to undergo CABG and receive medical therapy or to receive medical therapy alone. Left ventricular ejection fraction was measured at baseline and after 4 months of follow-up in 318 patients. The primary end point was death from any cause. The median duration of follow-up was 10.4 years.
CABG plus medical therapy was associated with a lower incidence of death from any cause than medical therapy alone (182 deaths among 298 patients in the CABG group vs. 209 deaths among 303 patients in the medical-therapy group; adjusted hazard ratio, 0.73; 95% confidence interval, 0.60 to 0.90). However, no significant interaction was observed between the presence or absence of myocardial viability and the beneficial effect of CABG plus medical therapy over medical therapy alone (P = 0.34 for interaction). An increase in left ventricular ejection fraction was observed only among patients with myocardial viability, irrespective of treatment assignment. There was no association between changes in left ventricular ejection fraction and subsequent death.
The findings of this study do not support the concept that myocardial viability is associated with a long-term benefit of CABG in patients with ischemic cardiomyopathy. The presence of viable myocardium was associated with improvement in left ventricular systolic function, irrespective of treatment, but such improvement was not related to long-term survival. (Funded by the National Institutes of Health; STICH ClinicalTrials.gov number, NCT00023595.).
The cues governing cardiac cell-fate decisions, cardiac differentiation, and three-dimensional morphogenesis are rapidly being elucidated. Several themes are emerging that are relevant for childhood ...and adult heart disease and the growing field of stem cell biology. This review will consider our current understanding of cardiac cell-fate determination and cardiogenesis—largely derived from developmental studies in model organisms and human genetic approaches—and examine future implications for diagnosis, prevention, and treatment of heart disease in the young and old.
Abstract Background Symptoms and survival of patients with carcinoid syndrome have improved, but development of carcinoid heart disease (CaHD) continues to decrease survival. Objectives This study ...aimed to analyze patient outcomes after valve surgery for CaHD during a 27-year period at 1 institution to determine early and late outcomes and opportunities for improved patient care. Methods We retrospectively studied the short-term and long-term outcomes of all consecutive patients with CaHD who underwent valve replacement at our institution between 1985 and 2012. Results The records of 195 patients with CaHD were analyzed. Pre-operative New York Heart Association class was III or IV in 125 of 178 patients (70%). All had tricuspid valve replacement (159 bioprostheses, 36 mechanical), and 157 underwent a pulmonary valve operation. Other concomitant operations included mitral valve procedure (11%), aortic valve procedure (9%), patent foramen ovale or atrial septal defect closure (23%), cardiac metastasectomies or biopsy (4%), and simultaneous coronary artery bypass (11%). There were 20 perioperative deaths (10%); after 2000, perioperative mortality was 6%. Survival rates (95% confidence intervals) at 1, 5, and 10 years were 69% (63% to 76%), 35% (28% to 43%), and 24% (18% to 32%), respectively. Overall mortality was associated with older age, cytotoxic chemotherapy, and tobacco use; 75% of survivors had symptomatic improvement at follow-up. Presymptomatic valve operation was not associated with late survival benefit. Conclusions Operative mortality associated with valve replacement surgery for CaHD has decreased. Symptomatic and survival benefit is noted in most patients when CaHD is managed by an experienced multidisciplinary team.
Cardiac-resynchronization therapy (CRT) benefits patients with left ventricular systolic dysfunction and a wide QRS complex. Most of these patients are candidates for an implantable ...cardioverter-defibrillator (ICD). We evaluated whether adding CRT to an ICD and optimal medical therapy might reduce mortality and morbidity among such patients.
We randomly assigned patients with New York Heart Association (NYHA) class II or III heart failure, a left ventricular ejection fraction of 30% or less, and an intrinsic QRS duration of 120 msec or more or a paced QRS duration of 200 msec or more to receive either an ICD alone or an ICD plus CRT. The primary outcome was death from any cause or hospitalization for heart failure.
We followed 1798 patients for a mean of 40 months. The primary outcome occurred in 297 of 894 patients (33.2%) in the ICD-CRT group and 364 of 904 patients (40.3%) in the ICD group (hazard ratio in the ICD-CRT group, 0.75; 95% confidence interval CI, 0.64 to 0.87; P<0.001). In the ICD-CRT group, 186 patients died, as compared with 236 in the ICD group (hazard ratio, 0.75; 95% CI, 0.62 to 0.91; P = 0.003), and 174 patients were hospitalized for heart failure, as compared with 236 in the ICD group (hazard ratio, 0.68; 95% CI, 0.56 to 0.83; P<0.001). However, at 30 days after device implantation, adverse events had occurred in 124 patients in the ICD-CRT group, as compared with 58 in the ICD group (P<0.001).
Among patients with NYHA class II or III heart failure, a wide QRS complex, and left ventricular systolic dysfunction, the addition of CRT to an ICD reduced rates of death and hospitalization for heart failure. This improvement was accompanied by more adverse events. (Funded by the Canadian Institutes of Health Research and Medtronic of Canada; ClinicalTrials.gov number, NCT00251251.).
The Fontan procedure is a successful palliation for children with single-ventricle physiology; however, many will eventually require heart transplantation. The purpose of this study was to determine ...risk factors for death awaiting transplantation and to examine results after transplantation in Fontan patients.
A retrospective, multi-institutional review was performed of 97 Fontan patients <18 years of age listed at 17 Pediatric Heart Transplant Study centers from 1993 to 2001. Mean age at listing was 9.7 years (0.5 to 17.9 years); 25% were <4 years old; 53% were United Network for Organ Sharing status 1; 18% required ventilator support. Pretransplantation survival was 78% at 6 months and 74% at 12 months and was similar to 243 children with other congenital heart disease (CHD) and 747 children without congenital heart disease (No-CHD), who were also awaiting transplantation. Patients who were younger, status 1, had shorter interval since Fontan, or were on a ventilator were more likely to die while waiting. At 6 months, the probability of receiving a transplant was similar for status 1 and 2 (65% versus 68%); however, the probability of death was higher for status 1 (22% versus 5%). Seventy patients underwent transplantation. Survival was 76% at 1 year, 70% at 3 years, and 68% at 5 years, slightly less than CHD and No-CHD patients. Causes of death included infection (30%), graft failure (17%), rejection (13%), sudden death (13%), and graft coronary artery disease (9%). Protein-losing enteropathy (present in 34 patients) resolved in all who survived >30 days after transplantation.
Heart transplantation is an effective therapy for pediatric patients with a failed Fontan. Although early posttransplantation survival is slightly lower than other patients with CHD, long-term results are encouraging, and protein-losing enteropathy can be expected to resolve.
ACC/AHA Task Force Members Glenn N. Levine, MD, FACC, FAHA, Chair Patrick T. O’Gara, MD, MACC, FAHA, Chair-Elect Jonathan L. Halperin, MD, FACC, FAHA, Immediate Past Chair¶ Sana M. Al-Khatib, MD, ...MHS, FACC, FAHA Joshua A. Beckman, MD, MS, FAHA Kim K. Birtcher, MS, PharmD, AACC Biykem Bozkurt, MD, PhD, FACC, FAHA¶ Ralph G. Brindis, MD, MPH, MACC¶ Joaquin E. Cigarroa, MD, FACC Anita Deswal, MD, MPH, FACC, FAHA Lesley H. Curtis, PhD, FAHA¶ Lee A. Fleisher, MD, FACC, FAHA Federico Gentile, MD, FACC Samuel Gidding, MD, FAHA¶ Zachary D. Goldberger, MD, MS, FACC, FAHA Mark A. Hlatky, MD, FACC, FAHA John Ikonomidis, MD, PhD, FAHA José A. Joglar, MD, FACC, FAHA Laura Mauri, MD, MSc, FAHA Barbara Riegel, PhD, RN, FAHA Susan J. Pressler, PhD, RN, FAHA¶ Duminda N. Wijeysundera, MD, PhD¶Former Task Force member; current member during the writing effort.Table of Contents Preamblee93 Introductione95 1.1.Methodology and Evidence Reviewe95 1.2.Organization of the Writing Committeee95 1.3.Document Review and Approvale95 1.4.Scope of the Guidelinee97 1.5.Abbreviationse99 2. Evidence Gaps and Future Research Needse182 Appendix 1 Author Relationships With Industry and Other Entities (Relevant)e214 Appendix 2 Reviewer Relationships With Industry and Other Entities (Comprehensive)e216 Preamble Since 1980, the American College of Cardiology (ACC) and American Heart Association (AHA) have translated scientific evidence into clinical practice guidelines with recommendations to improve cardiovascular health. Adherence to recommendations can be enhanced by shared decision-making between healthcare providers and patients, with patient engagement in selecting interventions based on individual values, preferences, and associated conditions and comorbidities.Methodology and Modernization The ACC/AHA Task Force on Clinical Practice Guidelines (Task Force) continuously reviews, updates, and modifies guideline methodology on the basis of published standards from organizations including the Institute of Medicine (P-1,P-2) and on the basis of internal reevaluation. Publication of new, potentially practice-changing study results that are relevant to an existing or new medication, device, or management strategy will prompt evaluation by the Task Force, in consultation with the relevant guideline writing committee, to determine whether a focused update should be commissioned.
Immune Privilege of Heart Valves Hill, Morgan Ashley; Kwon, Jennie H; Gerry, Brielle ...
Frontiers in immunology,
08/2021, Letnik:
12
Journal Article
Recenzirano
Odprti dostop
Immune privilege is an evolutionary adaptation that protects vital tissues with limited regenerative capacity from collateral damage by the immune response. Classical examples include the anterior ...chamber of the eye and the brain. More recently, the placenta, testes and articular cartilage were found to have similar immune privilege. What all of these tissues have in common is their vital function for evolutionary fitness and a limited regenerative capacity. Immune privilege is clinically relevant, because corneal transplantation and meniscal transplantation do not require immunosuppression. The heart valves also serve a vital function and have limited regenerative capacity after damage. Moreover, experimental and clinical evidence from heart valve transplantation suggests that the heart valves are spared from alloimmune injury. Here we review this evidence and propose the concept of heart valves as immune privileged sites. This concept has important clinical implications for heart valve transplantation.
Microarrays have been used extensively to profile transcriptome remodeling in failing human heart, although the genomic coverage provided is limited and fails to provide a detailed picture of the ...myocardial transcriptome landscape. Here, we describe sequencing-based transcriptome profiling, providing comprehensive analysis of myocardial mRNA, microRNA (miRNA), and long noncoding RNA (lncRNA) expression in failing human heart before and after mechanical support with a left ventricular (LV) assist device (LVAD).
Deep sequencing of RNA isolated from paired nonischemic (NICM; n=8) and ischemic (ICM; n=8) human failing LV samples collected before and after LVAD and from nonfailing human LV (n=8) was conducted. These analyses revealed high abundance of mRNA (37%) and lncRNA (71%) of mitochondrial origin. miRNASeq revealed 160 and 147 differentially expressed miRNAs in ICM and NICM, respectively, compared with nonfailing LV. Among these, only 2 (ICM) and 5 (NICM) miRNAs are normalized with LVAD. RNASeq detected 18 480, including 113 novel, lncRNAs in human LV. Among the 679 (ICM) and 570 (NICM) lncRNAs differentially expressed with heart failure, ≈10% are improved or normalized with LVAD. In addition, the expression signature of lncRNAs, but not miRNAs or mRNAs, distinguishes ICM from NICM. Further analysis suggests that cis-gene regulation represents a major mechanism of action of human cardiac lncRNAs.
The myocardial transcriptome is dynamically regulated in advanced heart failure and after LVAD support. The expression profiles of lncRNAs, but not mRNAs or miRNAs, can discriminate failing hearts of different pathologies and are markedly altered in response to LVAD support. These results suggest an important role for lncRNAs in the pathogenesis of heart failure and in reverse remodeling observed with mechanical support.
Aims
This randomized, double‐blind, placebo‐controlled trial assessed whether heart rate (HR) reduction with ivabradine improves cardiac function in heart failure with preserved ejection fraction ...(HFpEF).
Methods and results
The prEserveD left ventricular ejectIon fraction chronic heart Failure with ivabradine studY (EDIFY) included 179 patients in New York Heart Association (NYHA) classes II and III, in sinus rhythm, with HR of ≥70 b.p.m., NT‐proBNP of ≥220 pg/mL (BNP ≥80 pg/mL) and left ventricular ejection fraction of ≥45%. Ivabradine (or placebo) was titrated to 7.5 mg b.i.d. Patients were followed for 8 months on the change and assessed for three co‐primary endpoints: echo‐Doppler E/e′ ratio, distance on the 6‐min walking test (6MWT), and plasma NT‐proBNP concentration. At baseline, median E/e′ was 12.8 interquartile range (IQR): 9.9–16.3, median distance on the 6MWT was 320 m (IQR: 247–375 m), and median NT‐proBNP was 375 pg/mL (IQR: 253–701 pg/mL). Baseline median HR was 75 b.p.m. (IQR: 70–107 b.p.m.). A total of 171 patients (87 in the ivabradine group, 84 in the placebo group) were evaluated for treatment efficacy. After 8 months of treatment, findings showed a median change in HR of −13.0 b.p.m. (IQR: −18.0 to −6.0 b.p.m.) in the ivabradine group and −3.5 b.p.m. (IQR: −11.5 to 3.0 b.p.m.) in the placebo group estimated between‐group difference: 7.7 b.p.m.; 90% confidence interval (CI) −10 to −5.4; P < 0.0001. No evidence of improvement was found in any of the three co‐primary endpoints. There was almost no change in median E/e′ in either of the two groups median change: +1.0 (IQR: −0.8 to 2.9) in the ivabradine group; −0.6 (IQR: −2.2 to 1.4) in the placebo group; estimated between‐group difference: 1.4, 90% CI 0.3–2.5; P = 0.135. There were no meaningful changes in the other co‐primary endpoints and no apparent trends. There was no significant safety concern.
Conclusions
In patients with HFpEF, HR reduction with ivabradine did not improve outcomes. These findings do not support the use of ivabradine in HFpEF.
In addition to their anti-bacterial action, tetracyclines also have complex biological effects, including the modification of mitochondrial protein synthesis, metabolism and gene-expression. ...Long-term clinical studies have been performed using tetracyclines, without significant side effects. Previous studies demonstrated that doxycycline (DOX), a major tetracyclin antibiotic, exerted a protective effect in animal models of heart failure; however, its exact molecular mechanism is still unknown. Here, we provide the first evidence that DOX reduces oxidative stress-induced mitochondrial fragmentation and depolarization in H9c2 cardiomyocytes and beneficially alters the expression of Mfn-2, OPA-1 and Drp-1 -the main regulators of mitochondrial fusion and fission-in our isoproterenol (ISO)-induced heart failure model, ultimately decreasing the severity of heart failure. In mitochondria, oxidative stress causes a shift toward fission which leads to mitochondrial fragmentation and cell death. Protecting mitochondria from oxidative stress, and the regulation of mitochondrial dynamics by drugs that shift the balance toward fusion, could be a novel therapeutic approach for heart failure. On the basis of our findings, we raise the possibility that DOX could be a novel therapeutic agent in the future treatment of heart failure.
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