Youhua Zhang

Both Hypothyroidism and Hyperthyroidism Increase Atrial Fibrillation Inducibility in Rats

Background— Evidence indicates that cardiac hypothyroidism may contribute to heart failure progression. It is also known that heart failure is associated with an increased risk of atrial fibrillation (AF). Although it is established that hyperthyroidism increases AF incidence, the effect of hypothyroidism on AF is unclear. This study investigated the effects of different thyroid hormone levels, ranging from hypothyroidism to hyperthyroidism on AF inducibility in thyroidectomized rats. Methods and Results— Thyroidectomized rats with serum-confirmed hypothyroidism 1 month after surgery were randomized into hypothyroid (N=9), euthyroid (N=9), and hyperthyroid (N=9) groups. Rats received placebo, 3.3-mg L-thyroxine (T4), or 20-mg T4 pellets (60-day release form) for 2 months, respectively. At the end of treatment, hypothyroid, euthyroid, and hyperthyroid status was confirmed. Hypothyroid animals showed cardiac atrophy and reduced cardiac systolic and diastolic functions, whereas hyperthyroid rats exhibited cardiac hypertrophy and increased cardiac function. Hypothyroidism and hyperthyroidism produced opposite electrophysiological changes in heart rates and atrial effective refractory period, but both significantly increased AF susceptibility. AF incidence was 78% in hypothyroid, 67% in hyperthyroid, and the duration of induced AF was also longer, compared with 11% in the euthyroid group (all P<0.05). Hypothyroidism increased atrial interstitial fibrosis, but connexin 43 was not affected. Conclusions— Both hypothyroidism and hyperthyroidism lead to increased AF vulnerability in a rat thyroidectomy model. Our results stress that normal thyroid hormone levels are required to maintain normal cardiac electrophysiology and to prevent cardiac arrhythmias and AF.

Safe Oral Triiodo-L-Thyronine Therapy Protects from Post-Infarct Cardiac Dysfunction and Arrhythmias without Cardiovascular Adverse Effects

Background A large body of evidence suggests that thyroid hormones (THs) are beneficial for the treatment of cardiovascular disorders. We have shown that 3 days of triiodo-L-thyronine (T3) treatment in myocardial infarction (MI) rats increased left ventricular (LV) contractility and decreased myocyte apoptosis. However, no clinically translatable protocol is established for T3 treatment of ischemic heart disease. We hypothesized that low-dose oral T3 will offer safe therapeutic benefits in MI. Methods and Results Adult female rats underwent left coronary artery ligation or sham surgeries. T3 (~6 μg/kg/day) was available in drinking water ad libitum immediately following MI and continuing for 2 month(s) (mo). Compared to vehicle-treated MI, the oral T3-treated MI group at 2 mo had markedly improved anesthetized Magnetic Resonance Imaging-based LV ejection fraction and volumes without significant negative changes in heart rate, serum TH levels or heart weight, indicating safe therapy. Remarkably, T3 decreased the incidence of inducible atrial tachyarrhythmias by 88% and improved remodeling. These were accompanied by restoration of gene expression involving several key pathways including thyroid, ion channels, fibrosis, sympathetic, mitochondria and autophagy. Conclusions Low-dose oral T3 dramatically improved post-MI cardiac performance, decreased atrial arrhythmias and cardiac remodeling, and reversed many adverse changes in gene expression with no observable negative effects. This study also provides a safe and effective treatment/monitoring protocol that should readily translate to humans.

Long-term physiological T3 supplementation in hypertensive heart disease in rats.

Animal studies suggest that hypertension leads to cardiac tissue hypothyroidism, a condition that can by itself lead to heart failure. We have previously shown that short-term thyroid hormone treatment in Spontaneously Hypertensive Heart Failure (SHHF) rats near heart failure is beneficial. This study tested the hypothesis that therapeutic, long-term T3 treatment in SHHF rats can prevent or attenuate cardiac dysfunction. Female SHHF rats were treated orally with a physiological T3 dose (0.04 μg/ml) from 12 to 24 mo of age. Age-matched female SHHF and Wistar-Kyoto rats served as hypertensive and normotensive controls, respectively. SHHF rats had reduced serum free thyroid hormone levels and cardiac tissue T3 levels, LV dysfunction, and elevated LV collagen content compared with normotensive controls. Restoration of serum and cardiac tissue thyroid hormone levels in T3-treated rats was associated with no change in heart rate, but strong trends for improvement in LV systolic function and collagen levels. For instance, end-systolic diameter, fractional shortening, systolic wall stress, and LV collagen levels were no longer significantly different from controls. In conclusion, longstanding hypertension in rats led to chronic low serum and cardiac tissue thyroid hormone levels. Long-term treatment with low-dose T3 was safe. While cardiac dysfunction could not be completely prevented in the absence of antihypertensive treatment, T3 may offer additional benefits as an adjunct therapy with possible improvement in diastolic function.

Modified Low-Dose Triiodo-L-thyronine Therapy Safely Improves Function Following Myocardial Ischemia-Reperfusion Injury

Background: We have shown that thyroid hormones (THs) are cardioprotective and can be potentially used as safe therapeutic agents for diabetic cardiomyopathy and permanent infarction. However, no reliable, clinically translatable protocol exists for TH treatment of myocardial ischemia-reperfusion (IR) injury. We hypothesized that modified low-dose triiodo-L-thyronine (T3) therapy would confer safe therapeutic benefits against IR injury. Methods: Adult female rats underwent left coronary artery ligation for 60 min or sham surgeries. At 2 months following surgery and T3 treatment (described below), the rats were subjected to functional, morphological, and molecular examination. Results: Following surgery, the rats were treated with T3 (8 μg/kg/day) or vehicle in drinking water ad libitum following IR for 2 months. Oral T3 significantly improved left ventricular (LV) contractility, relaxation, and relaxation time constant, and decreased beta-myosin heavy chain gene expression. As it takes rats ~6 h post-surgery to begin drinking water, we then investigated whether modified T3 dosing initiated immediately upon reperfusion confers additional improvement. We injected an intraperitoneal bolus of T3 (12 μg/kg) upon reperfusion, along with low-dose oral T3 (4.5 μg/kg/day) in drinking water for 2 months. Continuous T3 therapy (bolus + low-dose oral) enhanced LV contractility compared with oral T3 alone. Relaxation parameters were also improved compared to vehicle. Importantly, these were accomplished without significant increases in hypertrophy, serum free T3 levels, or blood pressure. Conclusions: This is the first study to provide a safe cardiac therapeutic window and optimized, clinically translatable treatment-monitoring protocol for myocardial IR using commercially available and inexpensive T3. Low-dose oral T3 therapy supplemented with bolus treatment initiated upon reperfusion is safer and more efficacious.

Reduced epicardial vagal nerve density and impaired vagal control in a rat myocardial infarction–heart failure model

BACKGROUND Autonomic remodeling, characterized by sympathetic activation and vagal withdrawal, contributes to heart failure (HF) progression. However, the exact mechanism(s) responsible for vagal withdrawal in HF remain(s) unclear, and whether HF causes epicardial autonomic nerve remodeling is unknown. METHODS AND RESULTS Myocardial infarction (MI) was produced in 14 Sprague-Dawley rats, and 10 sham surgery rats served as the control. MI-HF was confirmed 2 months after the surgery by echocardiography and hemodynamic measurement. Cervical vagal nerve stimulation was delivered to examine the heart rate slowing effect. Whole heart acetylcholinesterase histochemistry was used to examine the epicardial autonomic nerve remodeling at dorsal ventricles (remote from the infarcted area). Compared with the control animals, the same vagal nerve stimulation had less heart rate slowing effect in MI-HF group. Both epicardial nerve bundle length-density (2.56±0.60 μm/mm2 versus 1.68±0.46 μm/mm2, P=.001) and branching point-density (1.24±0.25 points/mm2 versus 0.66±0.18 points/mm2, P<.001) were lower in MI-HF rats. The chemically stained epicardial nerve bundles contain both sympathetic (tyrosine hydroxylase positive) and vagal (choline acetyltransferase positive) fibers. However, within the stained nerve bundle, the chemical color corresponds mainly with the vagal fibers. CONCLUSIONS Whole heart acetylcholinesterase histochemistry revealed a decreased ventricular epicardial vagal nerve density in MI-HF rats, which may contribute to impaired cardiac vagal control in HF.

Sex‐related differences in intrinsic myocardial properties influence cardiac function in middle‐aged rats during infarction‐induced left ventricular remodeling

We previously determined that residual left ventricular (LV) myocardium of middle‐aged rats had sex‐related differences in regional tissue properties 4 weeks after a large myocardial infarction (MI). However, the impact of such differences on cardiac performance remained unclear. Therefore, our current study aimed to elucidate whether sex‐related changes in MI‐induced myocardial remodeling can influence cardiac function. A similar‐sized MI was induced in 12‐month‐old male (M‐MI) and female (F‐MI) Sprague–Dawley rats by ligation of the left coronary artery. The cardiac function was monitored for 2 months after MI and then various LV parameters were compared between sexes. We found that although two sex groups had a similar pattern of MI‐induced decline in LV function, F‐MI rats had greater cardiac performance compared to M‐MI rats, considering the higher values of EF (39.9 ± 3.4% vs. 26.7 ± 7.7%, P < 0.05), SW index (40.4 ± 2.1 mmHg • mL/kg vs. 20.2 ± 3.3 mmHg • mL/kg, P < 0.001), and CI (139.2 ± 7.9 mL/min/kg vs. 74.9 ± 14.7 mL/min/kg, P < 0.01). The poorer pumping capacity in M‐MI hearts was associated with markedly reduced LV compliance and prolonged relaxation. On the tissue level, F‐MI rats revealed a higher, than in M‐MI rats, density of cardiac myocytes in the LV free wall (2383.8 ± 242.6 cells/mm2 vs. 1785.7 ± 55.9 cells/mm2, P < 0.05). The latter finding correlated with a lower density of apoptotic cardiac myocytes in residual LV myocardium of F‐MI rats (0.18 ± 0.08 cells/mm2 vs. 0.91 ± 0.30 cells/mm2 in males, P < 0.01). Thus, our data suggested that F‐MI rats had markedly attenuated decline in cardiac performance compared to males due to ability of female rats to better retain functionally favorable intrinsic myocardial properties.

Comparison of Therapeutic Triiodothyronine Versus Metoprolol in the Treatment of Myocardial Infarction in Rats

BACKGROUND Beta blockers are standard therapy for myocardial infarction (MI). Preclinical studies have shown efficacy and safety of thyroid hormone (TH) treatment of cardiovascular disorders. Since THs interact with the sympathoadrenergic system, this study aimed to compare triiodothyronine (T3) and metoprolol (Met) in the treatment of rats with MI on pathophysiology and TH-adrenergic signaling. METHODS Female Sprague-Dawley rats aged 12 weeks underwent left anterior descending coronary artery ligation (MI) or sham surgeries. T3 (5 μg/kg/day) or Met (100 mg/kg/day) was given in drinking water immediately after surgery for eight weeks. At the terminal of the experiments, the rats were subjected to morphological, functional, and molecular examination. RESULTS T3 and Met significantly enhanced left ventricular contractility (left ventricular fractional shortening 21.37 ± 2.58% and 21.14 ± 3.71%, respectively) compared to untreated MI (17.88 ± 1.23%), and decreased the incidence of inducible atrial tachyarrhythmia by 87.5% and 62.5%, respectively. Although both treatments showed efficacy, T3 but not Met showed statistically significant improvements compared to MI in arrhythmia duration, left atrial diameter (T3 vs. MI 4.33 ± 0.63 vs. 5.65 ± 1.32 mm; p < 0.05), fibrosis (6.1 ± 0.6%, 6.6 ± 0.6% vs. 8.2 ± 0.7%, T3, Met vs. MI, respectively), and aortic vasorelaxation responsiveness to acetylcholine (pD2 6.97 ± 0.22, 6.83 ± 0.21 vs. 6.66 ± 0.22, T3, Met vs. MI, respectively). Quantitative polymerase chain reaction showed that T3 and Met attenuated expression of genes associated with inflammation and oxidative stress and restored expression of ion channels and contractile proteins. CONCLUSION These results support comparable efficacy of T3 and Met treatments, suggesting that T3 may provide a therapeutic alternative to standard β-receptor blockade, especially for patients intolerant to treatment with β-blockers after MI.

Failing Hearts Are More Vulnerable to Sympathetic, but Not Vagal Stimulation–Induced, Atrial Fibrillation—Ameliorated with Dantrolene Treatment

BACKGROUND Both vagal (VS) and sympathetic (SS) stimulations can increase atrial fibrillation (AF) inducibility, with VS being known as more arrhythmogenic in normal hearts. Heart failure (HF) results in autonomic dysfunction (characterized by sympathetic activation and vagal withdrawal) and is associated with an increased AF incidence. This study investigated whether failing hearts, compared with normal control hearts, respond differently to autonomic stimulation-induced AF arrhythmogenesis and the effect of dantrolene on SS-enhanced AF in HF. METHODS AND RESULTS A rat myocardial infarction (MI) HF model was used. In experiment 1, AF inducibility was compared in 9 MI-HF rats versus 10 sham-control animals at baseline, during VS, and during SS with isoproterenol infusion. In experiment 2, dantrolene treatment (n = 8) was compared with placebo-control (n = 9) on SS-induced AF inducibility in HF. Compared with the sham-control, baseline AF inducibility was higher in the MI-HF group. AF inducibility was augmented in both groups by autonomic stimulation. However, under VS the increased magnitude was less in the MI-HF group (49% ± 11% vs 80% ± 10%; P = .029), but under SS was significantly more (53% ± 8% vs 6% ± 7%; P < .001), compared with sham-control. Dantrolene significantly attenuated SS-enhanced AF in HF (69% ± 6% vs 29% ± 9%; P = .006). CONCLUSIONS Failing hearts are less sensitive to VS, but more vulnerable to SS-induced AF compared with normal-control hearts. Dantrolene can significantly attenuate SS-enhanced AF in HF, indicating that cardiac ryanodine receptor dysfunction may play a critical role in SS-enhanced AF in HF, and stabilizing leaky ryanodine receptor with the use of dantrolene may be a new treatment option in this condition.

Western diet triggers Toll-like receptor 4 (TLR4) signaling-induced endothelial dysfunction in female Wistar rats

Overconsumption of a diet rich in fat and carbohydrates, called the Western diet, is a major contributor to the global epidemic of cardiovascular disease. Despite previously documented cardiovascular protection exhibited in female rats, this safeguard may be lost under certain metabolic stressors. We hypothesized that female Wistar rats challenged by a Western diet composed of 21% fat and 50% carbohydrate (34.1% sucrose) for 17 wk would develop endothelial dysfunction via endothelial Toll-like receptor 4 (TLR4) signaling. Western diet-fed female rats exhibited dysregulation of metabolism, revealing increased body weight and abdominal fat, decreased expression of adiponectin in white adipose tissue, glucose intolerance, and impaired insulin sensitivity. Western diet exposure increased hepatic triglycerides and cholesterol alongside hepatic steatosis, categorizing nonalcoholic fatty liver disease. Moreover, a Western diet negatively affected vascular function, revealing hypertension, impaired endothelium-dependent vasorelaxation, aortic remodeling, and increased reactive oxygen species (ROS) production. Aortic protein expression of TLR4 and its downstream proteins were markedly increased in the Western diet-fed group in association with elevated serum levels of free fatty acids. In vitro experiments were conducted to test whether free fatty acids contribute to vascular ROS overproduction via the TLR4 signaling pathway. Cultured endothelial cells were stimulated with palmitate in the presence of TAK-242, a TLR4 signaling inhibitor. Palmitate-induced overgeneration of ROS in endothelial cells was abolished in the presence of TAK-242. Our data show that a Western diet induced endothelial dysfunction in female rats and suggest that endothelial TLR4 signaling may play a key role in abolishing female cardiovascular protection. NEW & NOTEWORTHY A Western diet induced elevated levels of free fatty acids, produced nonalcoholic fatty liver disease, and provoked endothelial dysfunction in female rats in association with Toll-like receptor 4 signaling-mediated vascular reactive oxygen species production. Limited consumption of a Western diet in premenopausal women may decrease their risk of cardiovascular complications.Overconsumption of a diet rich in fat and carbohydrates, called the Western diet, is a major contributor to the global epidemic of cardiovascular disease. Despite previously documented cardiovascular protection exhibited in female rats, this safeguard may be lost under certain metabolic stressors. We hypothesized that female Wistar rats challenged by a Western diet composed of 21% fat and 50% carbohydrate (34.1% sucrose) for 17 wk would develop endothelial dysfunction via endothelial Toll-like receptor 4 (TLR4) signaling. Western diet-fed female rats exhibited dysregulation of metabolism, revealing increased body weight and abdominal fat, decreased expression of adiponectin in white adipose tissue, glucose intolerance, and impaired insulin sensitivity. Western diet exposure increased hepatic triglycerides and cholesterol alongside hepatic steatosis, categorizing nonalcoholic fatty liver disease. Moreover, a Western diet negatively affected vascular function, revealing hypertension, impaired endothelium-dependent vasorelaxation, aortic remodeling, and increased reactive oxygen species (ROS) production. Aortic protein expression of TLR4 and its downstream proteins were markedly increased in the Western diet-fed group in association with elevated serum levels of free fatty acids. In vitro experiments were conducted to test whether free fatty acids contribute to vascular ROS overproduction via the TLR4 signaling pathway. Cultured endothelial cells were stimulated with palmitate in the presence of TAK-242, a TLR4 signaling inhibitor. Palmitate-induced overgeneration of ROS in endothelial cells was abolished in the presence of TAK-242. Our data show that a Western diet induced endothelial dysfunction in female rats and suggest that endothelial TLR4 signaling may play a key role in abolishing female cardiovascular protection. NEW & NOTEWORTHY A Western diet induced elevated levels of free fatty acids, produced nonalcoholic fatty liver disease, and provoked endothelial dysfunction in female rats in association with Toll-like receptor 4 signaling-mediated vascular reactive oxygen species production. Limited consumption of a Western diet in premenopausal women may decrease their risk of cardiovascular complications.

Thyroid dysfunction and atrial fibrillation: The role of myocardial hypothyroidism

A coarctation is very often deemed as a congenital anomaly which should be addressed surgically in infancy. Nevertheless, some adults are diagnosed with this anomaly when clinical signs of arterial hypertension come up. In the current era, the value of angiotomography for aortic coarctation in adults has increased and allowed cardiovascular surgeon to design an operative plan. In the setting of minimally invasive procedures for aortic diseases, endovascular approach has become standard choice aiming to reduce complications and mortality rate. It comes about that anatomic features of aortic coarctation are of paramount importance to determine feasibility and success rate of endovascular approach. The purpose of this abstract is to address surgical strategies to manage aortic coarctation in adults in case of inadequate anatomic profile. The proposition is to present some real cases and their operational plan with emphasis for extra-anatomic bypass and its principles and pitfalls.M prosthetic valve replacement requires lifelong anticoagulant therapy, although the optimal therapeutic range has been established. In this study, the dynamics of thrombin generation in patients underwent prosthetic valve replacement were monitored over a 2-year period using thrombin-antithrombin III complex (TAT), prothrombin fragment 1+2 (F1+2), D-dimer, and other blood coagulation-related factors such as warfarin concentration, vitamin K1-epoxide, and protein C activity. Platelet function was also assessed by maximum aggregation in response to adenosine diphosphate (2 μM), collagen (1 μg/mL) and arachidonic acids (0.6 μM). Blood samples were taken before the operation and 1, 6, 12, 24 months after the operation. The dose of warfarin was started at 3 mg/day and adjusted to control prothrombin time (PT)/international normalized ratio (INR) at around 2.0. After valve replacement, patients were treated with warfarin alone (n=4), warfarin in combination with an antiplatelet agent, ticlopidine (200 mg/day) (n=12) or warfarin and aspirin (81 mg/day) in combination (n=7). Before operation, levels of TAT and F1+2 and D-dimer were high, indicating enhanced thrombin generation and hyperfibrinolysis. Despite our anticoagulant and antiplatelet therapy, the levels of those parameters remained high during the first year after operation. However, by the end of the second year they decreased significantly and returned to within normal range as compared with those in the first year. Platelet function after the operation was suppressed to a similar degree irrespective of the antiplatelet agent used. Despite the low rate of embolism in our clinical experience, prosthetic valve replacement induces significant activation of the coagulation and fibrinolysis systems during the subsequent first year. However, activation of these systems subsides by the end of the second year, even on a program of low-intensity anticoagulation with low-dose antiplatelet agent.Sergey Suchkov1-4, Noel Rose7, Olga Golubnitschaja1,5, Katherine Payne8, Abner Notkins6, Yurii Belov3, Matt Springer11, Eduard Charchyan10 and Hiroyuki Abe9 1EPMA, EU 2A.I.Evdokimov Moscow State Medical & Dental University, Russia 3I.M.Sechenov First Moscow State Medical University, Russia 4UCC (United Cultural Convention), UK 5Rheinische Friedrich-Wilhelms-University of Bonn, Germany 6NIH, USA 7Johns Hopkins Medical Institutions, USA 8University of Manchester, UK 9ISPM, Japan 10Russian Academy of Sciences, Russia 11UCSF, USAMaterial and methods: I present the clinical case of a young woman patient 26 years old, who performed an EKG like screening test and discover unexpected a major left bundle branch block. She was asymptomatic except weakness. At the objective examination she presented rush around the eyes and a few red patch on the hands around metacarpo-phalangeal joints. BP = 130/80mmHg, HR =78bates/min rhythmic, splitting S2, vesicular sound normal. Laboratory tests were in normal range. Echocardiography of the heart was normal. The main problem was that this major left bundle branch block was acute or chronic and the etiology of this block. 1. A congenital major left bundle branch block could be but mention that the patient had performed one other EKG in the past at 18years and was normal so this was an acute major left bundle brunch block and wasn’t congenital because in this situation must to be present on the EKG in the past. 2. An unknown congenital heart disease could be other cause of the left bundle branch block but the auscultation of the heart, excepts plitting S2, not detect any systolic or diastolic murmur heart and echocardiography and echo-Doppler of the heart was normal and excluded this possibility. 3. Acute myocardial infarction under left bundle branch block theoretical could be but the patient didn’t presented chest pain and the level of cardiac enzymes: Troponin T, CPKMB, LDH was in normal range. 4. Post reptococus infection with streptococcus betahaemolitic group B could be other possibility but naso faringian secretion was negative, titre ASLO = 150,ESR=12/20, fibrinogen =234mg%, hemoleucograma =normal. So also this cause was excluded. 5. The autoimmune disease ESR, fibrinogen, PCR, CIC, C3, C4, antibody and double catena, lupus cells, ANCA negative. Because at the objective examination existed heliotrope rush and Gottron patch (spots) at the hands and she feel weakness I suspected dermatomiositis disease and was performed CPKMM, Autoantibody anti Mi2 was increase and anti Jo1was positives. A muscular biopsy was performed and after the histopathology examination was performed the result confirmed safe the diagnosis of dermatomiositisB hyperthyroidism and hypothyroidism can lead to heart failure (HF) development. HF is associated with an increased risk of atrial fibrillation (AF). While it is well established that hyperthyroidism increases AF incidence, the effect of hypothyroidism on AF is not so well recognized. To investigate the effect of altered thyroid status on AF inducibility, we treated thyroidectomized rats with placebo, 3.3mg L-thyroxine (T4), or 20 mg T4 pellets (60 day release form) for 2 months. At the end of treatment, hypothyroid, euthyroid, and hyperthyroid status was confirmed in the respective groups. Although hypothyroidism and hyperthyroidism had different effects on heart rate and cardiac function, both increased significantly AF susceptibility. AF inducibility was 78% in hypothyroid, 67% in hyperthyroid, compared with 11% in the euthyroid group (both p 40%) were randomized into T4 (n=14) and placebo (n=15) groups 2 weeks after MI and treated for 2 months. Compared with the placebo, T4 treatment attenuated atrial effective refractory period prolongation and reduced AF inducibility (AF/atrial flutter /tachycardia was inducible in 11/15 rats, or 73% in placebo vs 4/14 rats, or 29% in the T4 treated group, P<0.05). It is concluded that hypothyroidism, similar to hyperthyroidism, can lead to increased AF vulnerability in rats. Moreover, correcting myocardial tissue hypothyroidism with TH replacement therapy in HF may attenuate atrial remodeling and reduce AF inducibility post MI-HF. Clinical studies are still needed to confirm such benefits in patients.S amyloidoses are a group of rare diseases caused by deposition of protein fibrils. This talk will focus on major advances in the approaches to diagnosis, changing epidemiology and recent advances in treatment.Light chain (AL) amyloidosis remains the most frequently identified type but cardiac transthyretin amyloidosis is being increasingly recognised. Senile cardiac amyloidosis appears to be an epidemic awaiting diagnosis. Mass spectrometry using laser capture microdissection of a tiny amount of amyloid deposits from histological sections has enabled improved amyloid fibril typing. Understanding of proteotoxicity of amyloidogenic precursors has paved the way for new therapeutic approaches. Developments in cardiac magnetic resonance imaging such an Eq-CMR and T-1 mapping has led to accurate quantitation of the myocardial interstitial deposits for diagnosis and response assessment. 99mTc-DPD/PyP scintigraphy is transforming evaluation of cardiac amyloidosis. The availability of novel chemotherapy agents and better selection of patients for autologous stem cell transplantation have enabled the delivery of therapy in AL with less toxicity and improved outcomes. An array of novel agents, including RNA inhibitors, stabilisers of amyloid precursor proteins, inhibitors of fibril formation and immunotherapeutic targeting of amyloid deposits are all now in clinical development offering great hope for specific and effective new therapies.Methods: The RECOVER RIGHTTM is an FDA approved prospective, multicenter, single arm study that evaluates the safety and probable benefit of the Impella RPTM in patients with RVF refractory to medical treatment and deemed to require hemodynamic support. Two cohorts of patients were analyzed: Cohort A: Post Implantation from a durable LVAD and Cohort B: Post Cardiotomy or Post-MI Shock. Implantation inclusion criteria were as follows: Cardiac Index (CI) 15 mmHg or significant RV dysfunction on echocardiography. The primary endpoint was survival at 30 days or hospital discharge or next therapy. Secondary endpoints included hemodynamic improvement and decreased use of inotropes.