Sinan Simsir

Intramyocardial Injection of Autologous Cardiospheres or Cardiosphere-Derived Cells Preserves Function and Minimizes Adverse Ventricular Remodeling in Pigs With Heart Failure Post-Myocardial Infarction

OBJECTIVES The purpose of this study was to test the safety and efficacy of direct injection of cardiosphere-derived cells (CDCs) and their 3-dimensional precursors, cardiospheres, for cellular cardiomyoplasty in a mini-pig model of heart failure after myocardial infarction. BACKGROUND Intracoronary administration of CDCs has been demonstrated to reduce infarct size and improve hemodynamic indexes in the mini-pig model, but intramyocardial injection of CDCs or cardiospheres has not been assessed in large animals. METHODS Autologous cardiospheres or CDCs grown from endomyocardial biopsies were injected through thoracotomy 4 weeks after anteroseptal myocardial infarction. Engraftment optimization with luciferase-labeled CDCs guided the choice of cell dose (0.5 million cells/site) and target tissue (20 peri-infarct sites). Pigs were randomly allocated to placebo (n = 11), cardiospheres (n = 8), or CDCs (n = 10). Functional data were acquired before injection and again 8 weeks later, after which organs were harvested for histopathology. RESULTS Beyond the immediate perioperative period, all animals survived to protocol completion. Ejection fraction was equivalent at baseline, but at 8 weeks was higher than placebo in both of the cell-treated groups (placebo vs. CDC, p = 0.01; placebo vs. cardiospheres, p = 0.01). Echocardiographic and hemodynamic indexes of efficacy improved disproportionately with cardiospheres; likewise, adverse remodeling was more attenuated with cardiospheres than with CDCs. Provocative electrophysiologic testing showed no differences among groups, and no tumors were found. CONCLUSIONS Dosage-optimized direct injection of cardiospheres or CDCs is safe and effective in preserving ventricular function in porcine ischemic cardiomyopathy. Although CDCs and cardiospheres have equivalent effects on left ventricular ejection fraction, cardiospheres are superior in improving hemodynamics and regional function, and in attenuating ventricular remodeling.

Esophageal Motor Dysfunction and Gastroesophageal Reflux Are Prevalent in Lung Transplant Candidates

BACKGROUND Gastroesophageal reflux and aspiration contribute to the development of bronchiolitis obliterans and accelerate graft deterioration after lung transplantation (LTx). We evaluated LTx candidates for esophageal motor abnormalities and gastroesophageal reflux. METHODS Consecutive patients evaluated for LTx underwent 24-hour pH monitoring using a dual-channel pH probe and high-resolution esophageal manometry. High-resolution manometry was also performed in healthy control subjects. The prevalence of abnormal acid exposure was noted in the LTx candidates. RESULTS Thirty LTx candidates and 10 control subjects were evaluated. Lung transplantation candidates had higher residual upper and lower esophageal sphincter pressures. The mean proportion of peristaltic swallows was 21% lower in LTx candidates. Both hypotensive and aperistaltic swallows were sixfold more prevalent in LTx candidates than in control subjects. All control subjects had normal high-resolution manometry whereas 23 LTx candidates (76.7%) had esophageal peristaltic dysfunction. Abnormal acid exposure time was seen in the proximal and distal esophagus in 25% and 36% of LTx candidates, respectively. Lung transplantation candidates with idiopathic pulmonary fibrosis had more aperistaltic contractions, more negative minimum intrathoracic pressure, and a higher frequency of abnormal distal esophagus acid exposure. The majority of patients with complications after LTx demonstrated motor, anatomic, or pH abnormalities. CONCLUSIONS Disordered esophageal motor function and gastroesophageal reflux are common in LTx candidates. We believe high-resolution esophageal manometry is a valid tool to use and the abnormalities we identified may be representative of this unique patient population. The role of this study in predicting a worse outcome should be further studied in patients after LTx.

Use of Ventricular Assist Device as Bridge to Simultaneous Heart and Kidney Transplantation in Patients with Cardiac and Renal Failure

BACKGROUND Ventricular assist device (VAD) implantation as a bridge to cardiac transplantation is an effective treatment option for end-stage heart failure. Renal dysfunction is not uncommon but is considered to be a poor prognostic factor. We present our experience with 6 patients who had combined heart and kidney transplantation (HKT) after VAD implantation for advanced cardiac and renal failure. METHODS Of 74 patients who underwent VAD implantation as a bridge to transplant from May 2001 to September 2009, 28 patients developed renal failure, and of these, 6 (5 male, 1 female, ages 40-64 years) had HKT. All required hemodialysis because of renal failure before HKT. Immunosuppression consisted of anti-thymocyte globulin followed by triple drug therapy consisting of calcineurin inhibitors, mycophenolate, and corticosteroids. RESULTS Of the 6 HKT patients, 5 (83%) were alive without hemodialysis at 1 and 2 years; of the 22 patients with renal failure after VAD implantation without subsequent transplant, 1- and 2-year survivals were zero. Interval from VAD implantation to HKT ranged from 36 to 366 days (133 ± 127 days). At 6 months after HKT (100% alive), left ventricular ejection fraction was 60.2 ± 5.8% and serum creatinine 1.1 ± 0.2 mg/dL. Three HKT patients required temporary hemodialysis after surgery. Endomyocardial biopsy showed absence of ISHLT grade 2R-3A or greater cellular rejection, and none showed evidence of definite antibody-mediated rejection. CONCLUSIONS Based on our initial experience, simultaneous HKT is a safe treatment option with excellent outcomes for patients with advanced heart failure and persistent renal dysfunction after VAD implantation.

Heart transplantation using bivalirudin as anticoagulant

We present the case of a man with heparin-induced thrombocytopenia (HIT) and acute idiopathic decompensated cardiomyopathy who underwent successful heart transplantation with the use of bivalirudin as anticoagulant.

Heart allograft transplanted twice.

We present the case of a man who underwent successful heart transplantation with an allograft that was obtained from a donor who had already received heart transplantation.

Successful Combined Heart-Bilateral Lung-Kidney Transplantation From a Same Donor to Treat Severe Hypertrophic Cardiomyopathy With Secondary Pulmonary Hypertension and Renal Failure: Case Report and Review of the Literature

This study describes the first reported case of a combined heart-lung-kidney transplantation. Our patient suffered from hypertrophic cardiomyopathy due to long-standing hypertension with Dana Point Classification Group 2 pulmonary hypertension from the underlying cardiac disease, along with renal failure necessitating renal replacement therapy. Twenty months after the transplant procedure, she has stable pulmonary and renal function, plus has resumed a normal daily life with improving exercise tolerance. We propose that a combined heart-lung-kidney transplantation may be an acceptable therapeutic option for carefully selected patients with advanced, concomitant cardiac, pulmonary, and kidney disease.

Maximal care considerations when treating patients with end-stage heart failure: ethical and procedural quandaries in management of the very sick

Deciding who should receive maximal technological treatment options and who should not represents an ethical, moral, psychological and medico-legal challenge for health care providers. Especially in patients with chronic heart failure, the ethical and medico-legal issues associated with providing maximal possible care or withholding the same are coming to the forefront. Procedures, such as cardiac transplantation, have strict criteria for adequate candidacy. These criteria for subsequent listing are based on clinical outcome data but also reflect the reality of organ shortage. Lack of compliance and non-adherence to lifestyle changes represent relative contraindications to heart transplant candidacy. Mechanical circulatory support therapy using ventricular assist devices is becoming a more prominent therapeutic option for patients with end-stage heart failure who are not candidates for transplantation, which also requires strict criteria to enable beneficial outcome for the patient. Physicians need to critically reflect that in many cases, the patient’s best interest might not always mean pursuing maximal technological options available. This article reflects on the multitude of critical issues that health care providers have to face while caring for patients with end-stage heart failure.

Incidental Finding by Two-Dimensional Echocardiography of a Mycotic Pseudoaneurysm of the Ascending Aorta After Orthotopic Heart Transplantation

Mycotic pseudoaneurysm of the ascending aorta is a rare and potentially fatal complication of cardiac surgery, particularly in immunosuppressed heart transplantation patients. In this case, a 70-year-old man who underwent heart transplantation 4 months earlier was incidentally found to have a large pseudoaneurysm of the ascending aorta at the level of the aortic suture line. Surgical repair of the pseudoaneurysm was undertaken, and cultures from the pseudoaneurysm were found to be positive for Aspergillus fumigatus.

The New Concept of “Interventional Heart Failure Therapy”: Part 2—Inotropes, Valvular Disease, Pumps, and Transplantation

Recent advances in heart failure therapy include a variety of mechanical and device-based technologies that target structural aspects of heart failure that cannot be treated with drug therapy alone; these newer therapies can collectively be described as interventional heart failure therapy. This article is the second in a 2-part series reviewing interventional heart failure therapy. Interventions included in this discussion include those indicated for the treatment of end-stage refractory heart failure, including interventional medical therapy, interventional treatment of valvular disease, mechanical assist devices, and heart transplantation. Also included is a review of the currently available catheter-based pumps, which are intended to provide temporary support in patients with acute hemodynamic compromise. The use of cellular or stem cell therapy for the treatment of heart failure is an emerging interventional therapy and data supporting its use for the treatment heart failure will also be presented, as will a discussion of the role of palliative care and self-care in heart failure therapy.

Complicated ruptured sinus of Valsalva: cardiac computed tomographic angiography (64 slice) predicts surgical appearance and obviates need for invasive cardiac catheterization.

We present a case report of a ruptured sinus of Valsalva aneurysm (SVA) that presented as aortic insufficiency following bacterial endocarditits in a cardiac transplant patient. Cardiac computed tomographic angiography (CCTA) including volume rendered images predicted the appearance of the fistula entrance and defined spatial relationships facilitating the surgical approach. CCTA ability to define the coronary anatomy obviated the need for invasive coronary angiography. The use of this imaging modality especially with three-dimensional spatial visualization, and multiphase cine angiography can add significant value to the care of a patient with ruptured sinus of Valsalva.