Large animal models to study effectiveness of therapy devices in the treatment of heart failure with preserved ejection fraction (HFpEF).

Our understanding of the complex pathophysiology of Heart failure with preserved ejection fraction (HFpEF) is limited by the lack of a robust in vivo model. Existing in-vivo models attempt to reproduce the four main phenotypes of HFpEF; ageing, obesity, diabetes mellitus and hypertension. To date, there is no in vivo model that represents all the haemodynamic characteristics of HFpEF, and only a few have proven to be reliable for the preclinical evaluation of potentially new therapeutic targets. HFpEF accounts for 50% of all the heart failure cases and its incidence is on the rise, posing a huge economic burden on the health system. Patients with HFpEF have limited therapeutic options available. The inadequate effectiveness of current pharmaceutical therapeutics for HFpEF has prompted the development of device-based treatments that target the hemodynamic changes to reduce the symptoms of HFpEF. However, despite the potential of device-based solutions to treat HFpEF, most of these therapies are still in the developmental stage and a relevant HFpEF in vivo model will surely expedite their development process. This review article outlines the major limitations of the current large in-vivo models in use while discussing how these designs have helped in the development of therapy devices for the treatment of HFpEF.

Idiopathic Scrotal Calcinosis: A Case Report.

Idiopathic scrotal calcinosis is formation of calcium deposits in the dermal layers of the scrotum. It results in the formation of single or multiple nodular calcifications that vary in size and number. First reported in 1883, this condition is common in the third decade of life. The presenting complaints range from disfigurement to itching, leading to decreased quality of life. The diagnosis is usually made on a clinical basis and can be confirmed by the histopathology of the excised nodules. Surgical removal of the nodules is the generally recommended treatment. The surgery aims to eradicate the nodules leaving the scrotal skin enough for scrotoplasty. We present a case of idiopathic scrotal calcinosis in a 37 years old male who came for radiological examination.

Peri-Renal Lymphangiomatosis: A Case Report Presenting a Rare Disease at a Rarer Location.

Renal lymphangiomatosis is a rare pathology wherein dilatation of perirenal, parapelvic, and intrarenal lymphatics is observed and can occur in both children and adults. It has no gender predilection and can present in unilateral and bilateral forms. Clinical symptomatology ranges from incidental findings to flank pain, hematuria, and abdominal swelling. Radiological appearances may mimic renal cysts, peripelvic cysts, perinephric abscesses, or collections. This emphasizes the importance of developing familiarity with the imaging characteristics of this rare entity. We present the case of an 11-year-old boy whose chief complaint was abdominal distension and bilateral flank pain. The radiological assessment revealed bilateral perinephric collections, which, along with clinical correlation, led to the diagnosis of bilateral peri-renal lymphangiomatosis.

Alterations in Coronary Blood Flow and the Risk of Left Ventricular Distension in Venoarterial Extracorporeal Membrane Oxygenation.

Previous theoretical studies have suggested that veno-arterial extracorporeal membrane oxygenation (VA-ECMO) ought to consistently result in markedly increased left ventricular (LV) intracavitary pressures and volumes because of increased LV afterload. However, this phenomenon of LV distension does not universally occur and occurs only in a minority of cases. We sought to explain this discrepancy by considering the potential implications of VA-ECMO support on coronary blood flow and consequently improved LV contractility (the "Gregg" effect), in addition to the effects of VA-ECMO support upon LV loading conditions, in a lumped parameter-based theoretical circulatory model. We found that LV systolic dysfunction resulted in reduced coronary blood flow; VA-ECMO support augmented coronary blood flow proportionally to the circuit flow rate. On VA-ECMO support, a weak or absent Gregg effect resulted in increased LV end-diastolic pressures and volumes and increased end-systolic volume with decreased LV ejection fraction (LVEF), consistent with LV distension. In contrast, a more robust Gregg effect resulted in unaffected and/or even reduced LV end-diastolic pressure and volume, end-systolic volume, and unaffected or even increased LVEF. Left ventricular contractility augmentation proportional to coronary blood flow increased by VA-ECMO support may be an important contributory mechanism underlying why LV distension is observed only in a minority of cases.

Atrial Fibrillation Ablation-induced Pulmonary Venous Occlusion Requiring Pneumonectomy.

A 71-year-old woman with a history of atrial fibrillation underwent a catheter-based ablation procedure. Months later, she presented with dyspnea and a left-sided pleural effusion. Diagnostic evaluation revealed left-sided pulmonary venous occlusion, with essentially absent left lung perfusion. The patient underwent left pneumonectomy, with left atrial appendage occlusion. Although lobectomy for pulmonary venous occlusion of a single vein after pulmonary vein isolation has been described, this appears to be a novel report of occluded pulmonary venous drainage of an entire lung necessitating pneumonectomy.

Long-Term Outcomes of Allogeneic Hematopoietic Cell Transplantation in Patients with Newly Diagnosed Multiple Myeloma.

Despite remarkable progress in survival with the availability of novel agents, an overwhelming majority of patients with multiple myeloma (MM) have disease that relapses. Allogeneic (allo-) hematopoietic cell transplantation (HCT) is a potentially curative option for a subgroup of patients with high-risk MM. This study assessed the long-term outcome of MM patients who underwent allo-HCT while in first remission as consolidation treatment. Thirty-three patients with newly diagnosed MM who underwent allo-HCT as part of consolidation therapy between 1994 and 2016 were reviewed retrospectively. Of these patients, 70% underwent autologous HCT before allo-HCT. All patients were chemosensitive and achieved at least partial response before proceeding to allo-HCT. Most received nonmyeloablative/reduced-intensity conditioning (88%) and a matched sibling donor graft (85%). Acute graft-versus-host disease (GVHD) and chronic GVHD occurred in 30% and 61% of patients, respectively. The median duration of follow-up was 64.1 months (range, 1.4 to 199.2 months) for all patients and 164.4 months (range, 56.0 to 199.2 months) for survivors. The median progression-free survival (PFS) was 36 months (95% confidence interval (CI), 8.6 to 73.0 months). The median time from treatment to progression was 73.0 months (95% CI, 30.6 months to not reached). The median overall survival (OS) was 131.9 months (95% CI, 38.4 months to not reached). Of all patients, 39% were alive for more than 10 years, with 46% (n = 6) without progression or relapse. The cumulative incidence of relapse was 18% at 1 year, 39% at 5 years, and 46% at 10 years post-allo-HCT. The cumulative incidence of nonrelapse mortality was 3% at 100 days, 18% at 1 year, 21% at 3 years, and 24% at 5 year post-allo-HCT. On multivariable analysis, high-risk cytogenetics were associated with a shorter PFS (hazard ratio [HR], 2.7; 95% CI, 1.01 to 7.21; P = .047) and OS (HR, 4.91; 95% CI, 1.48 to 16.27; P = .009). Achieving complete remission after allo-HCT also was associated with longer PFS (HR, 0.24; 95% CI, 0.09 to 0.64; P = .004) and OS (HR, .23; 95% CI, .07 to .72; P = .012). Allo-HCT may confer a survival advantage in a selected population of MM patients when performed early in the disease course; additional data on identifying the patients who will benefit the most are needed.

Transient Osteoporosis of the Hip: A Radiologist's Perspective.

Transient osteoporosis of the hip (TOOH) is a rare disorder of unknown etiology without any antecedent history of trauma. There is a sudden onset of acute severe pain and temporary osteopenia in the joint involved with associated radiological findings of bone loss and marrow edema. Magnetic Resonance Imaging (MRI) is the gold standard imaging modality for diagnosis and disease monitoring. The major goal of this case presentation is to emphasize the necessity to add TOOH as an important differential of sudden hip pain and to review the literature on this entity.

Multi-institutional Analysis of 505 Patients With Coronavirus Disease-2019 Supported With Extracorporeal Membrane Oxygenation: Predictors of Survival.

BACKGROUND: We reviewed our experience with 505 patients with confirmed coronavirus disease-2019 (COVID-19) supported with extracorporeal membrane oxygenation (ECMO) at 45 hospitals and estimated risk factors for mortality. METHODS: A multi-institutional database was created and used to assess all patients with COVID-19 who were supported with ECMO. A Bayesian mixed-effects logistic regression model was estimated to assess the effect on survival of multiple potential risk factors for mortality, including age at cannulation for ECMO as well as days between diagnosis of COVID-19 and intubation and days between intubation and cannulation for ECMO. RESULTS: Median time on ECMO was 18 days (interquartile range, 10-29 days). All 505 patients separated from ECMO: 194 patients (38.4%) survived and 311 patients (61.6%) died. Survival with venovenous ECMO was 184 of 466 patients (39.5%), and survival with venoarterial ECMO was 8 of 30 patients (26.7%). Survivors had lower median age (44 vs 51 years, P < .001) and shorter median time interval from diagnosis to intubation (7 vs 11 days, P = .001). Adjusting for several confounding factors, we estimated that an ECMO patient intubated on day 14 after the diagnosis of COVID-19 vs day 4 had a relative odds of survival of 0.65 (95% credible interval, 0.44-0.96; posterior probability of negative effect, 98.5%). Age was also negatively associated with survival: relative to a 38-year-old patient, we estimated that a 57-year-old patient had a relative odds of survival of 0.43 (95% credible interval, 0.30-0.61; posterior probability of negative effect, >99.99%). CONCLUSIONS: ECMO facilitates salvage and survival of select critically ill patients with COVID-19. Survivors tend to be younger and have shorter time from diagnosis to intubation. Survival of patients supported with only venovenous ECMO was 39.5%.

Diuretic therapy in congestive heart failure.

In heart failure, fluid overload is a major pathological mechanism leading to vascular congestion, pulmonary congestion and elevated jugular venous pressures. Diuretics play a significant role in the management of patients with congestive heart failure. It is used to relieve the congestive symptoms of heart failure. However, the appropriate use of diuretics remains challenging due to various complications like electrolyte abnormalities, worsening renal function and diuretic resistance. This has prompted towards the search of safer and effective alternatives. This review evaluates the use of diuretics in congestive heart failure and discusses the complications of different types of diuretics, which is essential for successful management of congestion in patients with heart failure and hence to optimise the outcome for the patients.

Multi-institutional Analysis of 200 COVID-19 Patients Treated With Extracorporeal Membrane Oxygenation: Outcomes and Trends.

BACKGROUND: The role of extracorporeal membrane oxygenation (ECMO) in the management of patients with COVID-19 continues to evolve. The purpose of this analysis is to review our multi-institutional clinical experience involving 200 consecutive patients at 29 hospitals with confirmed COVID-19 supported with ECMO. METHODS: This analysis includes our first 200 COVID-19 patients with complete data who were supported with and separated from ECMO. These patients were cannulated between March 17 and December 1, 2020. Differences by mortality group were assessed using χ2 tests for categoric variables and Kruskal-Wallis rank sum tests and Welch's analysis of variance for continuous variables. RESULTS: Median ECMO time was 15 days (interquartile range, 9 to 28). All 200 patients have separated from ECMO: 90 patients (45%) survived and 110 patients (55%) died. Survival with venovenous ECMO was 87 of 188 patients (46.3%), whereas survival with venoarterial ECMO was 3 of 12 patients (25%). Of 90 survivors, 77 have been discharged from the hospital and 13 remain hospitalized at the ECMO-providing hospital. Survivors had lower median age (47 versus 56 years, P < .001) and shorter median time from diagnosis to ECMO cannulation (8 versus 12 days, P = .003). For the 90 survivors, adjunctive therapies on ECMO included intravenous steroids (64), remdesivir (49), convalescent plasma (43), anti-interleukin-6 receptor blockers (39), prostaglandin (33), and hydroxychloroquine (22). CONCLUSIONS: Extracorporeal membrane oxygenation facilitates survival of select critically ill patients with COVID-19. Survivors tend to be younger and have a shorter duration from diagnosis to cannulation. Substantial variation exists in drug treatment of COVID-19, but ECMO offers a reasonable rescue strategy.

Device-Based Solutions to Improve Cardiac Physiology and Hemodynamics in Heart Failure With Preserved Ejection Fraction.

Characterized by a rapidly increasing prevalence, elevated mortality and rehospitalization rates, and inadequacy of pharmaceutical therapies, heart failure with preserved ejection fraction (HFpEF) has motivated the widespread development of device-based solutions. HFpEF is a multifactorial disease of various etiologies and phenotypes, distinguished by diminished ventricular compliance, diastolic dysfunction, and symptoms of heart failure despite a normal ejection performance; these symptoms include pulmonary hypertension, limited cardiac reserve, autonomic imbalance, and exercise intolerance. Several types of atrial shunts, left ventricular expanders, stimulation-based therapies, and mechanical circulatory support devices are currently under development aiming to target one or more of these symptoms by addressing the associated mechanical or hemodynamic hallmarks. Although the majority of these solutions have shown promising results in clinical or preclinical studies, no device-based therapy has yet been approved for the treatment of patients with HFpEF. The purpose of this review is to discuss the rationale behind each of these devices and the findings from the initial testing phases, as well as the limitations and challenges associated with their clinical translation.

The role of anti-inflammatory drugs and nanoparticle-based drug delivery models in the management of ischemia-induced heart failure.

Ongoing advancements in the treatment of acute myocardial infarction (MI) have significantly decreased MI related mortality. Consequently, the number of patients experiencing post-MI heart failure (HF) has continued to rise. Infarction size and the extent of left ventricular (LV) remodeling are largely determined by the extent of ischemia at the time of myocardial injury. In the setting of MI or acute phase of post-MI LV remodeling, anti-inflammatory drugs including intravenous immunoglobulin (IVIG) and Pentoxifylline have shown potential efficacy in preventing post-MI remodeling in-vitro and in some clinical trials. However, systemic administration of anti-inflammatory drugs are not without their off-target side effects. Herein, we explore the clinical feasibility of targeted myocardial delivery of anti-inflammatory drugs via biodegradable polymers, liposomes, hydrogels, and nano-particle based drug delivery models (NDDM) based on existing pre-clinical and clinical models. We summarize the barriers to clinical application of targeted anti-inflammatory delivery post-MI, including challenges in achieving sufficient retention and distribution, as well as the potential need for multiple dosing. Collectively, we suggest that localized delivery of anti-inflammatory agents to the myocardium using NDDM is a promising approach for successful treatment of ischemic HF. Future studies will be instrumental in determining the most effective target and delivery modalities for orchestrating NDDM-mediated treatment of HF.

Multi-institutional Analysis of 100 Consecutive Patients with COVID-19 and Severe Pulmonary Compromise Treated with Extracorporeal Membrane Oxygenation: Outcomes and Trends Over Time.

The role of extracorporeal membrane oxygenation (ECMO) in the management of severely ill patients with coronavirus disease 2019 (COVID-19) continues to evolve. The purpose of this study is to review a multi-institutional clinical experience in 100 consecutive patients, at 20 hospitals, with confirmed COVID-19 supported with ECMO. This analysis includes our first 100 patients with complete data who had confirmed COVID-19 and were supported with ECMO. The first patient in the cohort was placed on ECMO on March 17, 2020. Differences by the mortality group were assessed using χ2 tests for categorical variables and Kruskal-Wallis rank-sum tests and Welch's analysis of variance for continuous variables. The median time on ECMO was 12.0 days (IQR = 8-22 days). All 100 patients have since been separated from ECMO: 50 patients survived and 50 patients died. The rate of survival with veno-venous ECMO was 49 of 96 patients (51%), whereas that with veno-arterial ECMO was 1 of 4 patients (25%). Of 50 survivors, 49 have been discharged from the hospital and 1 remains hospitalized at the ECMO-providing hospital. Survivors were generally younger, with a lower median age (47 versus 56.5 years, p = 0.014). In the 50 surviving patients, adjunctive therapies while on ECMO included intravenous steroids (26), anti-interleukin-6 receptor blockers (26), convalescent plasma (22), remdesivir (21), hydroxychloroquine (20), and prostaglandin (15). Extracorporeal membrane oxygenation may facilitate salvage and survival of selected critically ill patients with COVID-19. Survivors tend to be younger. Substantial variation exists in the drug treatment of COVID-19, but ECMO offers a reasonable rescue strategy.