Carlos M. Orrego

Cytokines and acute heart failure.

In patients with chronic heart failure, ongoing myocardial injury partially results from activation of the inflammatory system, with production and release of proinflammatory cytokines, activation of the complement system, production of autoantibodies, overexpression of major histocompatibility complex molecules, and expression of adhesion molecules that may perpetuate the inflammatory state. Acute decompensated heart failure modifies the course of chronic heart failure and worsens outcomes via a combination of potential mechanisms, including neurohormonal activation, apoptosis, and the inflammatory cascade. Proinflammatory cytokines, including tumor necrosis factor-&agr; and interleukin-6, play a pathogenetic role in chronic heart failure, and anti-inflammatory immune therapy is currently under investigation. In acute decompensation of chronic heart failure, the change in the inflammatory cytokine activation cascade is less clear. Larger investigational studies are needed to assess the exact roles of circulating and intracardiac cytokines in this particular patient population.

Percutaneous Placement of an Intra-Aortic Balloon Pump in the Left Axillary/Subclavian Position Provides Safe, Ambulatory Long-Term Support as Bridge to Heart Transplantation

OBJECTIVES This study evaluated the feasibility, tolerability, and efficacy of a strategy for percutaneous intra-aortic balloon pump (IABP) placement through the left axillary-subclavian artery to provide mechanical circulatory support in patients with end-stage heart failure as a bridge to heart transplantation. BACKGROUND The transfemoral approach to IABP placement is associated with major disadvantages, including the risk for infection and limitation of patient mobility in those requiring extended support. METHODS We developed a percutaneous technique for placing IABPs in the left axillary artery that permits upright sitting and ambulation. We performed a retrospective review of data from patients who had undergone left axillary IABP implantation between 2007 and 2012. RESULTS Fifty patients who received a left axillary IABP as a bridge to transplantation were identified, of whom 42 (84%) underwent heart or heart-multiorgan transplantation. Cumulative survival on IABP support was 92%, and post-transplant 90-day survival was 90%. Median duration of support was 18 days. Four of 50 patients (8%) died while on IABP support, and 3 (6%) received greater mechanical circulatory support. Four patients (8%) had clinically significant thromboembolic or bleeding events without long-term sequelae. The most common minor adverse event was IABP malposition, in 22 patients (44%). Prolonged IABP support in the heart-transplantation cohort was associated with significant improvements in mean pulmonary artery pressure and in creatinine and total bilirubin concentrations. CONCLUSIONS Percutaneous insertion of an IABP through the left axillary artery is a feasible and relatively well-tolerated strategy to bridge patients with end-stage heart failure to heart transplantation. This form of mechanical-device treatment permits upright sitting and ambulation in those requiring extended support.

Cellular Evidence of Reverse Cardiac Remodeling Induced by Cardiac Resynchronization Therapy

Left ventricular assist devices (LVADs) induce reverse cardiac remodeling by reducing myocyte size and collagen deposition. On the other hand, cardiac resynchronization therapy (CRT) induces reverse cardiac remodeling by improving electromechanical synchronization. The clinical and structural changes produced by CRT in failing myocardium are known, but whether these changes are accompanied by reverse cellular remodeling is unknown. A total of 12 patients with chronic heart failure (CHF) who underwent CRT and 15 patients who had LVAD therapy as clinically indicated and 8 healthy controls were compared. Demographics, echocardiographic data, and histologic samples from myocardial biopsies were analyzed and compared among groups. The authors found significant increases in myocyte size, myocardial fibrosis, and inflammation in both CHF groups who underwent CRT or LVAD, compared with healthy controls. After CRT or LVAD therapy, a significant decrease in myocyte size and tumor necrosis factor α (TNF-α) expression compared with healthy controls (P < .05) was found. In the CRT group, 6 of 8 patients demonstrated reduction in myocyte size and interstitial fibrosis. In addition, there was a decrease in myocyte size by 13%, total collagen by 27% and TNF-α by 49% in the CRT group vs 28%, 45%, and 45% in the LVAD group. CRT produces cellular reverse remodeling in failing human hearts that are comparable with those produced by LVAD therapy.

Atrial arrhythmias after lung transplant: Underlying mechanisms, risk factors, and prognosis

BACKGROUND Atrial arrhythmias (AAs) early after lung transplant are frequent and have a significant impact on morbidity and mortality. However, the pathogenesis of AAs after lung transplant remains incompletely understood. In this study we aimed to determine the prevalence of atrial fibrillation (AF) and other AAs, as well as risk factors, clinical outcomes and possible underlying mechanisms associated with AAs after lung transplant. METHODS A retrospective analysis was performed on 382 patients who underwent lung transplantation from 2000 to 2010. A 12-lead electrocardiogram (ECG) was obtained and AAs classified as AF and other AAs (atrial flutter [AFL] and supraventricular tachycardia [SVT]). Multivariate logistic regression analysis was performed to determine predictors, and Kaplan-Meier survival curves were constructed. RESULTS The incidence of AAs was 25%; 17.8% developed AF and 7.6% other AAs (AFL/SVT). The major indication for transplant was idiopathic pulmonary fibrosis (IPF, 35%). Significant predictors of AF were as follows: age; IPF; left atrial enlargement; diastolic dysfunction; and history of coronary artery disease (CAD). Risk factors for other AAs (AFL/SVT) were: age; right ventricle dysfunction; right ventricular enlargement; and elevated right atrial pressure (RAP). One-year mortality was higher in the arrhythmia group (21.5% arrhythmia vs 15.7% no-arrhythmia group; p < 0.05). In addition, patients treated with anti-arrhythmic medications had higher mortality (p < 0.05). CONCLUSIONS AAs are common after lung transplantation. Risk factors for developing either AF or other AAs (AFL/SVT) are different. The development of early AAs post-transplant is associated with prolonged post-operative stay and increased mortality. A rate-control strategy should be used as first-line therapy and anti-arrhythmic agents reserved for those patients who do not respond to the initial treatment.

Full Expression of Cardiomyopathy Is Partly Dependent on B‐Cells: A Pathway That Involves Cytokine Activation, Immunoglobulin Deposition, and Activation of Apoptosis

Background Limited information exists on the role of B‐cell‐dependent mechanisms in the progression of heart failure (HF). However, in failing human myocardium, there is evidence of deposition of activated complement components as well as anticardiac antibodies. We aimed to determine the contribution of B‐cells in HF progression using a nonsurgical mouse model of nonischemic cardiomyopathy (CMP). Methods and Results CMP protocol involved the use of l‐NAME and NaCl in the drinking water and angiotensin‐II infusion for 35 days. At day 35, mice were analyzed by cardiac magnetic resonance imaging, gene expression, and histology. Mice (12 weeks old) were divided into 4 groups, all in C57BL/6 background: wild‐type (WT) CMP; severe combined immunodeficiency (SCID) CMP (T‐ and B‐cell deficient); CD22− CMP (B‐cell depleted); and Nude CMP (T‐cell deficient), with their respective controls. We performed B‐cell depletion and reconstitution protocols. The protective effect of B‐cell depletion was demonstrated by a significant reduction of cell hypertrophy and collagen deposition and a preserved ejection fraction in the CD22− CMP group compared to WT CMP. Once SCID mice underwent B‐cell reconstitution with isolated CMP B‐cells, the CMP phenotype was restored. Furthermore, deposition of IgG3 and apoptosis in the myocardium follows the development of CMP; in addition, in vitro studies demonstrated that activated B‐cells stimulate collagen production by cardiac fibroblasts. Conclusions The absence of B‐cells in this model of HF resulted in less hypertrophy and collagen deposition, preservation of left ventricular function, and, in association with these changes, a reduction in expression of proinflammatory cytokines, immunoglobulin G deposition, and apoptosis in the myocardium. Taken together, these data suggest that B‐cells play a contributory role in an angiotensin‐II‐induced HF model.

Usefulness of routine surveillance endomyocardial biopsy 6 months after heart transplantation

BACKGROUND Endomyocardial biopsy (EMB) remains the gold standard for detecting rejection episodes in orthotopic heart transplant (OTH) patients. Follow-up protocols vary widely between transplant centers. At our center, we have implemented a conservative strategy protocol and here we report our outcomes. METHODS Patients from 2 cohorts were used for comparison analysis. OHT recipients from 1990 to 1995 comprised the standard strategy group, and those from 2004 to 2009 comprised the conservative strategy group. Survival outcomes and rejection episodes were compared between groups. RESULTS Mean age at OHT was 56 ± 10 years in the standard strategy group and 53 ± 10 years in the conservative strategy group. Both groups were predominantly composed of white men. The etiology of congestive heart failure was ischemic cardiomyopathy in more than 50% of the patients in both groups. From 6 to 12 months after OHT, we found that the number of episodes of rejection/total number of EMBs was 4.9% (8/163) in the standard group vs 2.0% (1/50) in the conservative group. From 12 to 24 months after transplant, the rate was 2.5% (8/320) in the standard group vs 11.9% (5/42) in the conservative group (p < 0.05). CONCLUSIONS Surveillance EMB after 6 months post-OHT in patients receiving contemporary immunosuppression is associated with a low yield of EMB-confirmed rejection in the absence of a clinical indication or echocardiographic findings that support clinical rejection. Most episodes of cellular rejection are mild and do not warrant treatment or a change in immunosuppression. The frequency of EMBs did not correlate with an increased risk of cardiac allograft vasculopathy or death.

Therapeutic plasma exchange a potential strategy for patients with advanced heart failure

Background: Previous reports had emphasized the importance of humoral immunity in heart failure in humans, primarily determined by the presence of circulating antibodies. However, there is little or no information about the frequency of anticardiac antibodies present in failing human myocardium. Methods: Clinical data and myocardial tissue samples were analyzed to determine the role of humoral immunity in patients with chronic heart failure (CHF) in different settings. Results: Anticardiac antibodies were found present in failing hearts but not in normal control hearts. Further, the level of expression of these anticardiac antibodies changed with the severity of the disease state; and in patients with acute heart failure, we found selective activation of B cells. Finally, treatment of CHF patients with therapeutic plasma exchange, a strategy that removes circulating antibodies, resulted in a reduction in anticardiac antibody deposition and improvements in cardiac function. Conclusion: These data collectively suggest a role of humoral immunity in the progression of heart failure. J. Clin. Apheresis, 2010.

MDCT assessment of mechanical circulatory support device complications

THE RISING NUMBER OF PATIENTS WITH ADVANCED HEART FAILURE WHO RECEIVE DURABLE MECHANICAL CIRCULATORY SUPPORT (MCS) DEVICES requires improved recognition of device complications [(1)][1]. Imaging is invariably needed because the clinical presentation is nonspecific. In our institution, we perform

Standardized extracts from black bean coats (Phaseolus vulgaris L.) prevent adverse cardiac remodeling in a murine model of non-ischemic cardiomyopathy

Black bean coats (Phaseolus vulgaris) contain bioactive compounds, including flavonoids and saponins, which have anti-fibrotic effects in which a standardized black bean extract (BBE) has been found to prevent liver fibrosis. Accordingly, the purpose of this study was to test whether BBE prevents remodeling in a murine model of non-ischemic cardiomyopathy. Saponins and flavonols were identified and quantified in BBE. Identification of flavonoids and saponins was confirmed by HPLC-MS-TOF. The cardiomyopathy model was produced by administering angiotensin and oral supplementation of L-NAME. Experimental animals received BBE in their diet at a dose equivalent to 40 mg per kg per day. The cardiomyopathy group (CMP) was characterized by severe maladaptive remodeling, left ventricular (LV) hypertrophy, decreased ejection fraction and increased LV end-diastolic volume. CMP mice treated with BBE had an improvement in ventricular function and reduction in LV mass. In addition, we found 65%, 85% and 83% reductions in interstitial fibrosis, brain natriuretic peptide (BNP) and transforming growth factor (TGFβ) expression, respectively. Consistent with those observations, collagen and TGFβ expression by isolated cardiac fibroblasts was reduced 82% and 70% following administration of BBE. BBE prevents adverse cardiac remodeling by reducing the extent of fibrosis and collagen deposition that occur in cardiomyopathy. These initial studies provide the basis for future research into the therapeutic potential of BBE in heart failure.

An unusual case of right-sided heart failure caused by giant sinus of Valsalva aneurysm obstructing right ventricular outflow tract.

A 63-year-old male with a previous history of leg swelling for many decades and dyspnoea on exertion for few months, presented to the local emergency department complaining of unexpected fall. He was found to have a systolic murmur and abnormal ECG for which he was referred to our clinic for further evaluation. His physical examination was significant for a loud ejection systolic murmur at the left upper sternal border, an elevated jugular venous pressure and bilateral lower extremity oedema with significant venous stasis changes. An ECG showed normal sinus rhythm with incomplete RBBB. Transthoracic …