Advanced Heart Failure: Therapeutic Options and Challenges in the Evolving Field of Left Ventricular Assist Devices.

Heart Failure is a chronic and progressively deteriorating syndrome that has reached epidemic proportions worldwide. Improved outcomes have been achieved with novel drugs and devices. However, the number of patients refractory to conventional medical therapy is growing. These advanced heart failure patients suffer from severe symptoms and frequent hospitalizations and have a dismal prognosis, with a significant socioeconomic burden in health care systems. Patients in this group may be eligible for advanced heart failure therapies, including heart transplantation and chronic mechanical circulatory support with left ventricular assist devices (LVADs). Heart transplantation remains the treatment of choice for eligible candidates, but the number of transplants worldwide has reached a plateau and is limited by the shortage of donor organs and prolonged wait times. Therefore, LVADs have emerged as an effective and durable form of therapy, and they are currently being used as a bridge to heart transplant, destination lifetime therapy, and cardiac recovery in selected patients. Although this field is evolving rapidly, LVADs are not free of complications, making appropriate patient selection and management by experienced centers imperative for successful therapy. Here, we review current LVAD technology, indications for durable MCS therapy, and strategies for timely referral to advanced heart failure centers before irreversible end-organ abnormalities.

Prospective Phenotyping of Right Ventricle Function Following Intra-Aortic Balloon Pump Counterpulsation in Left Ventricular Assist Device Candidates: Outcomes and Predictors of Response.

Intra-aortic balloon pump (IABP) may be applied to optimize advanced heart failure (AHF) patients and improve right ventricular (RV) function before left ventricular assist device (LVAD) implantation. We aimed to evaluate the outcome of this intervention and define RV response predictors. Decompensated AHF patients, not eligible for LVAD because of poor RV function, who required IABP for stabilization were enrolled. Echocardiography and invasive hemodynamics were serially applied to determine fulfillment of prespecified "LVAD eligibility RV function" criteria (right atrium pressure [RA] <12 mm Hg, pulmonary artery pulsatility index [PAPi] >2.00, RA/pulmonary capillary wedge pressure [PCWP] <0.67, RV strain <-14.0%). Right ventricular-free wall tissue was harvested to assess interstitial fibrosis. Eighteen patients (12 male), aged 38 ± 14 years were supported with IABP for 55 ± 51 (3-180) days. In 11 (61.1%), RV improved and fulfilled the prespecified criteria, while seven (38.9%) showed no substantial improvement. Histopathology revealed an inverse correlation between RV interstitial fibrosis and functional benefit following IABP: interstitial fibrosis correlated with post-IABP RA ( r = 0.63, p = 0.037), RA/PCWP ( r = 0.87, p = 0.001), PAPi ( r = -0.83, p = 0.003). Conclusively, IABP improves RV function in certain AHF patients facilitating successful LVAD implantation. Right ventricular interstitial fibrosis quantification may be applied to predict response and guide preoperative patient selection and optimization. http://links.lww.com/ASAIO/A995.

Phenotype Characterization and Course of Patients With Arrhythmogenic Right Ventricular Cardiomyopathy and Biventricular Advanced Heart Failure: A Report of 3 Cases.

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) may be complicated by heart failure. Management of advanced heart failure in this context is challenging. METHODS: We reviewed our center's experience with advanced heart failure therapies in patients with ARVC. Three rapidly deteriorating patients with ARVC with biventricular heart failure were found. Their management and outcomes are presented. Data on ventricular fibrosis were available in 2 of them and are also included. RESULTS: The first patient underwent initially successful paracorporeal pulsatile biventricular assist device (BiVAD) implantation. However, a large ischemic stroke occurred 2 weeks later, and the patient died after 2 months. The second patient underwent urgent BiVAD implantation after extracorporeal membrane oxygenation support because of cardiogenic shock, but his course was complicated by multiorgan failure due to systemic infection and the patient died. The last patient, being at Interagency Registry for Mechanically Assisted Circulatory Support 3-4 profile, underwent heart transplant with uneventful recovery. Extensive fibrosis was present in both ventricles of 2 patients undergoing pathology examination. CONCLUSIONS: Patients with ARVC and advanced biventricular heart failure are characterized by extensive ventricular fibrosis and considerable risk, but data on their management are limited. Biventricular circulatory support is associated with suboptimal outcomes, and prioritization for heart transplant seems preferable.

The effect of paracorporeal pulsatile biventricular assist devices on allosensitization in adults: A comparison with left ventricular assist devices.

Ventricular assist devices (VADs) have been associated with the development of anti-HLA antibodies ('allosensitization'), but data on devices providing biventricular support in adults are limited. We sought to characterize differences in anti-HLA antibody formation in adult patients receiving left- (LVAD) versus biventricular- (BiVAD) assist devices as bridge to transplantation (BTT) by retrospectively reviewing the records of adult patients who have undergone VAD implantation at our institution. We assessed 82 patients supported with a pulsatile-flow paracorporeal BiVAD and compared them with 40 patients receiving LVAD till 2018. Forty-eight (58.5%) of the BiVAD and 23 (57.5%) of the LVAD patients were eventually transplanted (p = 0.91) with an average time to transplantation 559 and 598 days, respectively (p = 0.73). Evidence of sensitization pre-VAD was found in 11.0% of the BiVAD patients and 15.0% of the LVAD ones (p = 0.53); these percentages rose to 43.9% (p < 0.001) and 40.0% (p = 0.01), respectively. The post-VAD sensitization status was not significantly different between the BiVAD and the LVAD group (p = 0.68). De novo sensitization was comparable between the two groups (p = 0.55). Post-transplantation outcomes regarding rejections and cardiac allograft vasculopathy were also similar. Conclusively, BiVAD- and LVAD- induced allosensitization do not appear to differ significantly.

A modern approach to aortic valve insufficiency: Aortic root restoration via HAART 300 internal annuloplasty ring.

BACKGROUND AND AIM OF THE STUDY: HAART 300 is an internal geometric annuloplasty ring. The safety and efficacy of this novel device in aortic valve (AV) repair in a single referral center are reported. METHODS: Twenty patients with trileaflet AV insufficiency with ascending aorta and/or aortic root enlargement were included. Subannular implantation was performed to correct annular dilatation, whereas concomitant leaflet repair was performed whenever required. All but two patients also received ascending aorta replacement, whereas selective sinus replacement was performed in all but five patients. RESULTS: Follow-up was for a maximum of 3.8 years and a mean of 2.2 years. Mean age was 54.2 years old. Moderate to severe preoperative AV insufficiency was noted in 75% of patients, whereas 70% of them had an ascending aorta over 45 mm. One patient was lost from follow-up. Overall mortality as well as major complication rates were zero. Early postoperatively, no more than mild AV regurgitation was detected, whereas only one patient appeared with moderate AV regurgitation during our 2.2-year follow-up. New York Heart Association class was also significantly lower compared to preoperative values and valve gradients remained low at last follow-up. CONCLUSIONS: Geometric ring annuloplasty is a safe and effective valve sparing approach to deal with AV insufficiency contributing to overall root reconstruction. Short-term results are excellent rendering this easily reproducible and versatile method very attractive.

Q Fever Endocarditis and a New Genotype of Coxiella burnetii, Greece.

Underdiagnosis of Coxiella burnetii infections in Greece is possible because of lack of awareness by physicians, and most suspected cases are in patients with no bovine contact. We found serologic evidence of C. burnetii infection throughout Greece and identified a new C. burnetii genotype in the aortic valve of a patient with Q fever endocarditis.

68-year-old woman with paroxysmal atrial fibrillation.

We present the case of a 68-year-old woman, currently asymptomatic but with a history of paroxysmal atrial fibrillation and tachycardia-bradycardia syndrome, for which she underwent a DDD pacemaker implantation and was started on oral anticoagulants. A recent chest X-ray (figure 1), for respiratory infection, was performed and the patient was referred to our institution for evaluation. Following diagnostic procedures, the patient was successfully operated on. heartjnl;105/8/656/F1F1F1Figure 1Preoperative chest X-ray (A) and chest CT with contrast (B). QUESTION: What is the most likely diagnosis?Mitral stenosis.Pericardial cyst.Left atrial appendage aneurysm.Left atrial myxoma.Atrial septal defect.

Serum and tissue biomarkers in aortic stenosis.

BACKGROUND: Calcific aortic valve stenosis (CAVS) is seen in a large proportion of individuals over 60 years. It is an active process, influenced by lipid accumulation, mechanical stress, inflammation, and abnormal extracellular matrix turnover. Various biomarkers (BMs) are studied, as regards mechanisms, diagnosis and prognosis. METHODS: In the calcified valves calcium deposition, elastin fragmentation and disorganization of cellular matrix were assessed, together with expression of OPN, OPG, osteocalcin (OCN) and RL2. We prospectively studied the following serum BMs in 60 patients with CAVS and compared them to 20 healthy controls, free from any cardiac disease: Matrix metalloproteinases (MMP) 2 and 9 and tissue inhibitor of metalloproteinase 1 (TIMP1), which regulate collagen turnover, inflammatory factors, i.e. tumor necrosis factor a (TNFa), interleukin 2 (IL2), transforming growth factor ß1 (TGF-ß1) which regulates fibrosis, fetuin-A (fet-A), osteopontin (OPN), osteoprotegerin (OPG), sclerostin (SOST), and relaxin-2 (RL2) which positively or negatively regulate calcification. Monocyte chemoattractant protein 1 (MCP-1) which regulates migration and infiltration of monocytes/macrophages was also studied as well as malondialdehyde (MDA) an oxidative marker. RESULTS: Extent of tissue valve calcification (Alizarin Red stain) was negatively correlated with tissue elastin, and RL2, and positively correlated with tissue OCN and serum TIMP1 and MCP-1 and negatively with MMP9. Tissue OCN was positively correlated with OPN and negatively with the elastin. Tissue OPN was negatively correlated with elastin and OPG. Tissue OPN OPG and RL2 were not correlated with serum levels In the serum we found in patients statistically lower TIMP1, fet-A and RL2 levels, while all other BMs were higher compared to the healthy group. Positive correlations between SOST and IL2, OPG and MDA but negative with TNFa and OPN were found; also MMP9 was negatively correlated with TNFa and MCP-1 was negatively correlated with TIMP1. CONCLUSION: We found that many BMs expressing calcification, collagen breakdown, or formation, and inflammation are increased in the valve tissue and in the serum of patients with CAVS as compared with healthy group. Our findings may give new insights towards diagnosis but also therapy. Thus antisclerostin, and antiflammatory agents could be tried for preventing aortic calcification progression.

Left ventricular pseudoaneurysm formation: Two cases and review of the literature.

Left ventricular wall rupture (LVWR) comprises a complication of acute myocardial infarction (AMI). Acute LVWR is a fatal condition, unless the formation of a pseudoaneurysm occurs. Several risk factors have been described, predisposing to LVWR. High index of suspicion and imaging techniques, namely echocardiography and computed tomography, are the cornerstones of timely diagnosis of the condition. As LVWR usually leads to death, emergency surgery is the treatment of choice, resulting in significant reduction in mortality and providing favorable short-term outcomes and adequate prognosis during late follow-up. Herein, we present two patients who were diagnosed with LVWR following AMI, and subsequent pseudoaneurysm formation. In parallel, we review the aforementioned condition.

Inhaled nitric oxide plus iloprost in the setting of post-left assist device right heart dysfunction.

BACKGROUND: Pulmonary hypertension and right ventricular (RV) dysfunction may complicate the implantation of a left ventricular assist device (LVAD). We examined whether inhaled vasodilators can sufficiently reduce RV afterload, avoiding the need for temporary RV mechanical support. METHODS: The study includes 7 patients with RV dysfunction after LVAD insertion. Treatment consisted of inotropes, inhaled nitric oxide (10 ppm), and iloprost (10 µg) in repeated doses. Full hemodynamic profile was obtained before inhalation, during administration of inhaled NO alone (before and after iloprost), as well as after the first two doses of inhaled iloprost. Tricuspid annular velocity was estimated at baseline and before and after adding iloprost. RESULTS: There was a statistically significant reduction in pulmonary vascular resistance (PVR), mean pulmonary artery pressure (MPAP), RV systolic pressure, and pulmonary capillary wedge pressure, and a considerable increase in LVAD flow, LV flow rate index, and tricuspid annular velocity at all points of evaluation versus baseline. By the end of the protocol, MPAP/mean systemic arterial pressure, and PVR/systemic vascular resistance ratios were reduced by 0.17±0.03 (95% confidence interval, 0.10 to 0.25, p=0.001) and 0.12±0.025 (95% confidence interval, 0.06 to 0.18; p=0.003), respectively. The tricuspid annular velocity increased by 2.3±0.18 cm/s (95% confidence interval, 1.83 to 2.73 cm/s; p<0.001). Pairwise comparisons before and after iloprost showed an important decrease in PVR (p=0.022), MPAP (p=0.001), pulmonary capillary wedge pressure (p=0.002), and RV systolic pressure (p<0.001), and a rise in tricuspid annular velocity (p=0.008). CONCLUSIONS: Inhaled vasodilators mainly affected the pulmonary vasculature. Combination treatment with inhaled NO and iloprost sufficiently decreased PVR and MPAP on the basis of an additive effect, improved RV function, and avoided the need for RV assist device.

Carotid shunt provides cerebral protection during emergency coronary artery bypass grafting in a patient with bilateral high grade carotid stenosis: a case report.

BACKGROUND: Management of patients with co-existent coronary and carotid disease is a controversial and challenging issue. The risk for stroke after coronary artery bypass grafting (CABG) in patients with hemodynamically significant carotid stenosis is up to 30%. In these patients a common practice is to proceed first with the restoration of cerebral perfusion and then perform the coronary revascularization. The rationale is that this strategy will reduce perioperative neurological morbidity and mortality. However, what happens when the carotid procedure is acutely complicated by cardiac instability which necessitates the interruption of the carotid procedure? CASE REPORT: We describe a case of a patient with unstable angina and high grade asymptomatic bilateral carotid stenosis who underwent emergency combined CABG and carotid endarterectomy (CEA). Due to hemodynamic instability, ST-T changes, hypotension and bradycardia, upon completion of endarterectomy we placed a carotid shunt and the patient was put on cardiopulmonary bypass through median sternotomy. After triple CABG (duration of 90 minutes) we concluded the interrupted CEA procedure with primary closure of the carotid arteriotomy with the shunt in place. The postoperative course was uneventful and the patient was discharged after a week. In extreme cases with bilateral severe carotid stenosis and coronary artery disease where the carotid procedure should be interrupted, we suggest the use of carotid shunt which can provide adequate cerebral perfusion giving time to cardiac surgeon to perform the life saving cardiac procedure first.

Stented within a stentless aortic valve. A simple surgical solution for the replacement of a stentless aortic bioprosthesis.

Stentless aortic bioprostheses are designed to offer better hemodynamics, less mechanical stress to the leaflets and as a result less degeneration. Although encouraging results are reported, little evidence has been published regarding reoperations of stentless valves. We are reporting a case of a structural valve dysfunction of an O'Brien-Angell stentless prosthesis, which could not be extracted during reoperation without damaging the aortic root. We are presenting a simple, quick and effective surgical solution, the surgical 'valve within a valve' technique for the avoidance of a redo complex root procedure.

Bile leakage presenting as acute abdomen due to a stone created around a migrated surgical clip.

BACKGROUND: Surgical clips may migrate into the common bile duct after surgery for cholecystolithiasis leading to usually early or middle-term complications. CASE REPORT: A 31-year-old woman, 6 years after laparoscopic cholecystectomy, developed acute abdomen and choloperitoneum after rupture of a secondary bile duct and bile leakage. This complication was due to a solitary common bile duct stone. The stone was formed around a surgical clip that had migrated from the cystic duct remnant to the common bile duct. The patient underwent investigative laparotomy and, subsequently, an ERCP with stone extraction and clearance of the common bile duct. She was perfectly well at the follow-up after 14 months. CONCLUSIONS: Rupture of a bile duct and biliary peritonitis may be a delayed complication of laparoscopic cholecystectomy due to surgical clip migration and formation of a stone. Definitive treatment of the condition may be achieved through ERCP. Surgeons, gastroenterologists and radiologists should be aware of this late complication of laparoscopic cholecystectomy in cases of acute abdomen.

LigaSure versus clamp-and-tie thyroidectomy for benign nodular disease.

BACKGROUND: LigaSure is an alternative bipolar diathermy system (BDS) combining vessel sealing with reduced thermal spread, which has been successfully used in many abdominal operations; however, there is a little experience in open thyroidectomy. This study compares the efficacy and the advantages of the LigaSure BDS when used for total thyroidectomy for benign thyroid disease with the conventional clamp-and-tie technique. METHODS: Between May 1998 and October 2002, 517 patients underwent total thyroidectomy for benign thyroid multinodular goiter. Among them, from May 1998 until May 2000, 247 patients (group I) were operated on with the conventional clamp-and-tie technique, whereas from May 2000 until October 2003, 270 patients (group II) underwent total thyroidectomy for benign multinodular goiter with LigaSure BDS through a 4-cm transverse suprasternal incision. Demographics, pathologic characteristics, gland mass, operative time, blood loss, and complications were assessed. RESULTS: There were no intraoperative complications. Thyroid mass was similar in both groups, but the operative time was shorter in group II than in group I (mean +/- standard deviation, 71 +/- 14 minutes vs 86 +/- 22 minutes; p < .01). Intraoperative total blood loss was similar between the two groups, but postoperative drain volume was less in group II than in group I (21 +/- 15 mL; p < .01). Major post-thyroidectomy complications (ie, laryngeal nerve palsy, hematoma, and hypocalcemia) occurred less frequently in the LigaSure group than in the clamp-and-tie group (0.7%, 0.4%, 1.1% vs 4%, 2%, 4.8%, respectively; p < .05). The mean +/- standard deviation postoperative hospital stay was significantly less for the patients in group II than for those in group I (2.3 +/- 1.7 days vs 2.8 +/- 1.3 days; p < .05). CONCLUSIONS: The use of the LigaSure vessel sealer for thyroid surgery is an effective and safe alternative that reduces the overall operative time and could be successfully applied through a narrow surgical incision.

Video-assisted thoracoscopic surgery for thoracic empyema: primarily, or after fibrinolytic therapy failure?

BACKGROUND: Traditional and modern treatments are proposed for thoracic empyema. The efficacy of video-assisted thocoscopic surgery (VATS) has been studied when the method is applied either as primary treatment for thoracic empyema or after the failure of fibrinolytic therapy. METHODS: Thirty-eight patients treated with VATS for thoracic empyema have been reviewed. Of those, 20 patients (group 1) with empyema thoracis were referred to VATS after failure of the fibrinolytic treatment. Another 18 patients (group 2) with primary empyema thoracis were treated thoracoscopically immediately when empyema was diagnosed. Both groups were staged 5, 6, or 7 according to Light's criteria. RESULTS: The group 2 patients showed a higher empyema resolving rate (95% versus 85%), shorter hospital stay (4.5 versus 7.5 days), and significantly shorter duration of the procedure (70 +/- 14 versus 62 +/- 10 minutes) in comparison with the patients of group 1. CONCLUSIONS: The VATS technique for thoracic empyema is a well-tolerated, minimally invasive technique, with excellent therapeutic results, mild postoperative complications, and reduced hospitalization. VATS should be considered as the treatment of choice for thoracic empyema, in the fibrinopurulent stage, as it is more effective when applied primarily than when applied after fibrinolytic therapy.

Hyperglycemia attenuates erythromycin-induced acceleration of liquid-phase gastric emptying of hypertonic liquids in healthy subjects.

Acute hyperglycemia has been associated with delayed gastric emptying in healthy controls. Erythromycin has recently been found to be a gastrointestinal prokinetic agent in both solids and hypertonic liquids. Our aim was to examine whether the acute steady-state hyperglycemia reduces the erythromycin-induced acceleration of gastric emptying of hypertonic liquids after a fasted state of the stomach in healthy subjects. In 12 healthy subjects scintigraphic measurement of gastric emptying of a hypertonic radiolabeled liquid meal, during normoglycemia (5-8.9 mmol/l glucose) or induced hyperglycemia (16-19 mmol/liter glucose) by intravenous glucose infusion after giving either placebo or 200 mg intravenous erythromycin, was performed on four separate days in random order. In the hyperglycemic state compared with normoglycemia, either after placebo administration or erythromycin, the gastric emptying of the hypertonic liquid was reduced. The lag-phase duration was significantly increased (17.5 +/- 5.5 min, and 7.2 +/- 4.5 min vs 10.5 +/- 3.4 min, and 3.5 +/- 2.5 min, respectively, P < 0.0001) as were the overall T1/2 (gastric emptying time of the half meal) (52.5 +/- 13 min and 24.5 +/- 5.5 min vs 42 +/- 10.5 min, and 16 +/- 6 min, respectively, P < 0.0001) and the percentage of liquid meal retained in the stomach at 60 and 100 min postprandially (P < 0.001). In conclusion, hyperglycaemia attenuates the acceleration effect of erythromycin and decreases the overall gastric emptying rate of hypertonic liquids in healthy subjects.