The Impact on Medical Students of the 9/11 Attacks on New York's World Trade Center.

Phenomenon: Little is known about how participation in disaster relief impacts medical students. During the terror attacks of September 11, 2001, New York Medical College School of Medicine students witnessed the attacks and then became members of emergency treatment teams at St. Vincent's Hospital, the trauma center nearest to the World Trade Center. To date, only two reports describe how 9/11 influenced the lives of medical students. This study was designed to characterize the short- and long-term effects on NYMC students and to compare those effects between students assigned to St Vincent's Hospital and classmates assigned to rotations at facilities more remote from the attack site. We hypothesized that participation in direct relief efforts by students assigned to the St. Vincent's site might have long-lasting effects on their lives and these effects might vary when compared to classmates assigned elsewhere. Approach: This was a retrospective, survey-based, unmatched cohort study. Participants included all school of medicine graduates who were St. Vincent's rotators on 9/11 (N = 22) and classmates (N = 24) assigned to other sites who could be contacted and agreed to participate. Our primary measure was whether the 9/11 experience affected the participant's life, defined as an affirmative response to the item which asked whether the 9/11 experience affected the participant's "life thereafter, career choice, attitudes toward life or attitudes toward practice." Secondary measures included self-reported effects on career, life, attitudes, health, resilience, personal growth, personality features, and the temporal relationship between the attack and stress symptoms. Findings: Completed surveys were received from 16/22 (73%) St. Vincent's and 18/24 (75%) non-Saint Vincent's participants: 62% male, 82% had children, 74% identified as Caucasian/white and 76% employed full-time. Overall, slightly more than half (58%) of respondents reported an effect of 9/11 on their life, with a greater but non-significant proportion of St. Vincent's rotators reporting life impact (67% versus 50% for St. Vincent's versus other locations, respectively). High post-9/11 stress levels, current marriage, and ability to make and keep family and social relationships were associated with an effect on life which approached statistical significance. Participants reported positive or no post 9/11 effects on empathy and altruism (50%), resilience (47%), attitudes toward medical practice and career (32%), and charitable giving (24%), while positive, negative, or no effects were reported for attitude toward life, family and social relations, physical health, and conscientiousness. Mental health was the only domain in which all participants reported unchanged or negative effects. Two St. Vincent's rotators but no students assigned elsewhere believed they experienced 9/11-related post-traumatic stress disorder. Insights: Just over half of New York Medical College School of Medicine students rotating at St. Vincent's Hospital on 9/11 or elsewhere reported significant life-effects as a result of direct/indirect experiences related to the attack. Perceived stress may have been a more important driver of this life-change than other factors such as geographic proximity to the disaster site and/or direct participation in relief efforts. Further study of medical school interventions focused on stress reduction among students who participate in disaster relief is warranted.

Impact of weight on the efficacy and safety of direct-acting oral anticoagulants in patients with non-valvular atrial fibrillation: a meta-analysis.

AIMS: This study sought to determine the impact of weight and body mass index (BMI) on the safety and efficacy of direct-acting oral anticoagulants (DOACs) compared with warfarin in patients with non-valvular atrial fibrillation. METHODS AND RESULTS: A systematic literature search was employed in PubMed, Embase, and Cochrane clinical trials with no language or date restrictions. Randomized trials or their substudies were assessed for relevant outcome data for efficacy that included stroke or systemic embolization (SSE), and safety including major bleeding and all-cause mortality. Binary outcome data and odds ratios from the relevant articles were used to calculate the pooled relative risk. For SSE, the data from the four Phase III trials showed that DOACs are better or similarly effective with low BMI 0.73 (0.56-0.97), normal BMI 0.72 (0.58-0.91), overweight 0.87 (0.76-0.99), and obese 0.87 (0.76-1.00). The risk of major bleeding was also better or similar with DOACs in all BMI subgroups with low BMI 0.62 (0.37-1.05), normal BMI 0.72 (0.58-0.90), overweight 0.83 (0.71-0.96), and obese 0.91 (0.81-1.03). There was no impact on mortality in all the subgroups. In a meta-regression analysis, the effect size advantage of DOACs compared with warfarin in terms of safety and efficacy gradually attenuated with increasing weight. CONCLUSION: Our findings suggest that a weight-based dosage adjustment may be necessary to achieve optimal benefits of DOACs for thromboembolic prevention in these patients with non-valvular atrial fibrillation. Further dedicated trials are needed to confirm these findings. PROSPERO 2019 CRD42019140693. Available from: https://www.crd.york.ac.uk/prospero/display_record.php? ID=CRD42019140693.

Cardiogenic shock during heart failure hospitalizations: Age-, sex-, and race-stratified trends in incidence and outcomes.

The objectives were to study the overall and age-, sex-, and race-stratified incidence of cardiogenic shock (CS) during heart failure hospitalizations (HFHs) not complicated by acute coronary syndromes (ACS), utilization of short-term mechanical circulatory support (MCS) and in-hospital mortality with non-ACS-related CS, and respective temporal trends. Data are lacking regarding the epidemiology of non-ACS-related CS during HFHs. METHODS: Retrospective observational analysis of the National Inpatient Sample 2005-2014 to identify all HFHs in adult patients without concomitant ACS. RESULTS: Of 8,333,752 HFHs, incidence rate of non-ACS-related CS was 8.7 per thousand HFHs (N = 72,668), a 4-fold increase from 4.1 to 15.6 per thousand HFHs between 2005 and 2014 (Ptrend < .001). Among those with non-ACS-related CS, utilization rates of intra-aortic balloon pump, extracorporeal membrane oxygenation, and temporary ventricular assist devices were 12.8%, 1.4%, and 2.5%, respectively. Respective 2005 to 2014 trends were 14.2% to 10.7%, 0.6% to 1.8%, and 0.8% to 2.7% (Ptrend for all, <.001). In-hospital mortality rate was 27.1%, with a substantial decrease from 42.4% in 2005 to 23.3% in 2014 (Ptrend < .001). These temporal trends were largely consistent across age, sex, and race subgroups. CONCLUSION: During HFHs in the United States, non-ACS-related CS occurred infrequently but was associated with substantial mortality. Non-ACS-related CS incidence and certain MCS utilization rates increased, and in-hospital mortality rate decreased between 2005 and 2014. These trends were generally homogenous across the age, sex, and race groups. The observed trends in incidence and mortality may be a reflection of increased identification of CS during HFHs, although further study is needed to assess whether temporal changes in care may have influenced outcomes.

Cardiovascular Abnormalities in Carbon Monoxide Poisoning.

Acute carbon monoxide (CO) poisoning is the most common cause of poisoning and poisoning-related death in the United States. It manifests as broad spectrum of symptoms ranging from mild headache, nausea, and fatigue to dizziness, syncope, coma, seizures resulting in cardiovascular collapse, respiratory failure, and death. Cardiovascular complications of CO poisoning has been well reported and include myocardial stunning, left ventricular dysfunction, pulmonary edema, and arrhythmias. Acute myocardial ischemia has also been reported from increased thrombogenicity due to CO poisoning. Myocardial toxicity from CO exposure is associated with increased short-term and long-term mortality. Carboxyhemoglobin (COHb) levels do not correlate well with the clinical severity of CO poisoning. Supplemental oxygen remains the cornerstone of therapy for CO poisoning. Hyperbaric oxygen therapy increases CO elimination and has been used with wide variability in patients with evidence of neurological and myocardial injury from CO poisoning, but its benefit in limiting or reversing cardiac injury is unknown. We present a comprehensive review of literature on cardiovascular manifestations of CO poisoning and propose a diagnostic algorithm for managing patients with CO poisoning.

Use of Diuretics in the Treatment of Heart Failure in Older Adults.

Diuretics are the most commonly prescribed class of drugs in patients with heart failure, and in the short term they remain the most effective treatment for relief from fluid congestion. This article reviews the mode of action of the various diuretic classes and the physiologic adaptations that follow and sets up the basis for their use in the treatment of volume-retaining states, particularly as applies to the elderly. In addition, the article reviews the common side effects related to diuretics.

Regional variation in the incidence and outcomes of in-hospital cardiac arrest in the United States.

BACKGROUND: Regional variation in the incidence and outcomes of in-hospital cardiac arrest (IHCA) is not well studied and may have important health and policy implications. METHODS AND RESULTS: We used the 2003 to 2011 Nationwide Inpatient Sample databases to identify patients≥18 years of age who underwent cardiopulmonary resuscitation (International Classification of Diseases, Ninth Edition, Clinical Modification procedure codes 99.60 and 99.63) for IHCA. Regional differences in IHCA incidence, survival to hospital discharge, and resource use (total hospital cost and discharge disposition among survivors) were analyzed. Of 838,465 patients with IHCA, 162,270 (19.4%) were in the Northeast, 159,581 (19.0%) were in the Midwest, 316,201 (37.7%) were in the South, and 200,413 (23.9%) were in the West. Overall IHCA incidence in the United States was 2.85 per 1000 hospital admissions. IHCA incidence was lowest in the Midwest and highest in the West (2.33 and 3.73 per 1000 hospital admissions, respectively). Compared with the Northeast, risk-adjusted survival to discharge was significantly higher in the Midwest (odds ratio, 1.33; 95% confidence interval, 1.31-1.36), South (odds ratio, 1.21; 95% confidence interval, 1.19-1.23), and West (odds ratio, 1.25; 95% confidence interval, 1.23-1.27). IHCA survival increased significantly from 2003 to 2011 in the United States and in all regions (all Ptrend<0.001). Total hospital cost was highest in the West, whereas discharge to skilled nursing facility and use of home health care among survivors was highest in the Northeast. CONCLUSIONS: We observed significant regional variation in IHCA incidence, survival, and resource use in the United States. This variation was explained only partially by differences in patient and hospital characteristics. Further studies are needed to identify other potential factors responsible for these regional differences to improve outcomes after IHCA.

Type B Lactic Acidosis Associated With Venlafaxine Overdose.

Lactic acidosis that is not secondary to tissue hypoperfusion or hypoxemia (type B lactic acidosis) is a rare but potentially fatal condition that has been associated with drugs like metformin, linezolid, and nucleoside reverse-transcriptase inhibitors in patients with HIV. We report the first case of type B lactic acidosis caused by overdose of the serotonin-norepinephrine reuptake inhibitor, venlafaxine. A 55-year-old man with no significant medical history was brought to the emergency department after intentional ingestion of around 80 capsules of venlafaxine (a total dose of over 6000 mg) in an attempt to commit suicide. Complete blood count and comprehensive metabolic panel were unremarkable except for a bicarbonate level of 13 mEq/L and an anion gap of 22 mEq/L. An arterial blood gas revealed a pH of 7.39, partial pressure of CO2 of 19 mm Hg, calculated bicarbonate of 11.5 mEq/L, and a lactate level of 8.6 mmol/L. The patient was started on aggressive intravenous hydration with normal saline along with oral activated charcoal with sorbitol. Repeat laboratory work after 4 hours showed an improvement in anion gap (15 mEq/L) and serum lactate (5.6 mmol/L). The patient remained stable throughout the hospital stay and lactic acidosis resolved in 24 hours. In the absence of hypotension, hypoxemia, kidney or liver dysfunction, myopathy, malignancy, or use of other medications, venlafaxine was the most likely cause of lactic acidosis in our case. Rapid improvement of acidosis was probably related to clearance of the drug.

New and Emerging LDL Cholesterol-Lowering Drugs.

The role of low-density lipoprotein cholesterol (LDL-C) in the pathophysiology of atherosclerosis is well recognized, and the use of LDL-C lowering medications has led to a significant reduction of cardiovascular risk in both primary and secondary prevention. Statins are the standard of care and their use is supported by extensive evidence demonstrating their effectiveness in lowering LDL-C and in reducing the risk for cardiovascular disease. However, many individuals at risk for cardiovascular disease fail to achieve LDL-C goals. In addition, several patients are intolerant to statins due to side effects, mostly myalgia and weakness, especially at high statin doses. However, until recently, the efficacy of other non-statin LDL-C-lowering drugs was modest, not exceeding a LDL-C reduction of 20%. In view of the above, extensive research is being carried out to identify new LDL-C-lowering agents with an acceptable side effect profile, which, used alone or in combination with statins, would improve our ability to achieve LDL-C goals and reduce cardiovascular risk. This review aims to provide the current evidence regarding the newly approved LDL-C-lowering agents, as well as the clinical and scientific data pertaining to promising new and emerging LDL-C-lowering drugs on the horizon.

The Role of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers in Postangioplasty Restenosis.

Postangioplasty restenosis remains a clinical problem, and various strategies have been used to minimize or eliminate this complication. Stimulation of the renin-angiotensin system has been shown to cause vascular smooth muscle migration, matrix deposition, and endothelial dysfunction, which are possible causes of postangioplasty restenosis, suggesting that the use of angiotensin-converting enzyme (ACE) inhibitors and/or angiotensin receptor blockers might ameliorate or prevent restenosis. However, data obtained to date in both animal and human studies of various designs show conflicting results regarding the benefit or lack of benefit of angiotensin inhibition strategies. It has also been shown that the type of ACE genotype may influence the effects of drugs on restenosis, suggesting that in the future, a pharmacogenetic approach might be of use for augmenting the benefit in patients from inhibitors of the angiotensin system. As of now, there are no supportive data to suggest a benefit of using routine ACE inhibitors or angiotensin receptor blockers to prevent postangioplasty restenosis in the general population.

The role of nonpharmacologic device interventions in the management of drug-resistant hypertension.

Resistant systemic hypertension in patients is defined as the inability to control blood pressure despite taking at least three antihypertensive drugs, one of which is a diuretic. Two nonpharmacologic approaches are being evaluated in resistant hypertensive patients. First, the Rheos® Baroreflex Hypertension Therapy system is an implantable device that activates the carotid baroreflex through electrical stimulation of the carotid sinus wall. Sustained and clinically lower blood pressure has been observed in patient clinical trials. The second approach is a catheter-based strategy which denervates the renal afferent and efferent autonomic nervous system. This strategy has also been shown to be effective in drug-resistant patients, and has also been shown to decrease renin production, preserve renal function, improve glucose tolerance, and reduce left ventricular hypertrophy. Both carotid sinus stimulation and renal denervation are now being evaluated in clinical trials for the long-term control of hypertension.

Thrombotic and Vascular Complications of Oral Contraceptives.

The oral contraceptive pill is the most commonly used form of reversible contraception, as it has significantly grown in popularity in recent years. The 2 types of oral contraceptive pills are combination oral contraceptives, which contain estrogen and progesterone, and progestin-only pills. Both have failure rates of approximately 7.2-9% with typical use and are safe for most patients. However, several thrombotic and vascular complications have been found to be associated with the usage of oral contraceptive pills, most notably being an increase in blood pressure and thrombosis. Although these complications do not typically affect young, healthy females, they merit concern for patients with a history of hypertension or thrombosis or patients with preexisting risk factors for these conditions. Overall, progestin-only pills are the safer option regarding these complications. Additionally, a complete summary of the medical eligibility criteria for contraceptive use has been created and is regularly updated by the Centers for Disease Control and Prevention. This chart summarizes the recommendations for contraception use by patients with a variety of preexisting conditions or risk factors.

Multisystem Inflammatory Syndrome in Children during the COVID-19 Pandemic: A Review of Clinical Manifestations, Cardiac Complications and Medical Management.

The SARS-CoV-2 pandemic has led to widespread research on associated clinical syndromes. While pediatric patients were initially deemed as a low-risk population for severe COVID-related disease, an increasing number of case reports have revealed a rare but potentially life-threatening syndrome, multisystem inflammatory syndrome in children (MIS-C). MIS-C is hypothesized to be due to hyperactivation of the immune system via a cytokine storm which leads to end-organ damage via endothelial dysfunction and changes in vascular permeability. Laboratory studies have displayed increased inflammatory markers such as C-reactive protein, erythrocyte sedimentation rate, D-dimer, tumor necrosis factor-alpha, and various interleukins. Studies have reported a wide range of clinical manifestations, including but not limited to fever, hypotension, shock, rash, coagulopathy, and gastrointestinal distress. Cardiac imaging and screening tests have revealed several complications, such as left ventricular failure, arrhythmias, and pericardial effusions. Medical management of MIS-C and cardiac sequelae have included supportive care, intravenous immunoglobulins, and corticosteroids, as well as immunomodulators, monoclonal antibodies, aspirin, and therapeutic anticoagulation, which have prevented serious outcomes in the majority of pediatric patients. Future multicenter and large-scale research is required for precise risk-stratification of MIS-C as well as long-term monitoring of sequelae. In this review, we aim to (1) outline the laboratory findings and clinical manifestations of MIS-C, and (2) describe cardiac complications and medical management of MIS-C.

Zilebesiran: A Promising Antihypertensive Therapy Inhibiting Angiotensinogen Synthesis.

Systemic hypertension is one of the most common noncommunicable diseases globally, with over one billion people affected. Despite the widespread use of numerous antihypertensive drugs, it is estimated that only a fifth of diagnosed patients achieve adequate blood pressure control. For this reason, the pursuit for novel antihypertensive therapies is ongoing. Zilebesiran, an siRNA designed to target the liver, is the newest potential addition to the renin-angiotensin-aldosterone system-inhibiting drugs. This subcutaneous injection post-transcriptionally silences the AGT gene responsible for the synthesis of angiotensinogen. By preventing the progenitor protein of the renin-angiotensin-aldosterone system, zilebesiran blocks the downstream production of angiotensin II, which plays multiple roles in blood pressure elevation. Phase I clinical trials have demonstrated a dose-dependent negative relationship between zilebesiran and blood pressure/serum angiotensinogen levels-with sustained effects up to 6 months. Researchers also demonstrated a promising safety profile, as most of the adverse events were mild to moderate in nature. Phase II trials assessing efficacy and optimal dosing are currently underway, with a predicted completion by 2025.

A Review of Terlipressin in Hepatorenal Syndrome: Targeting Endothelial Dysfunction and Subsequent Cardiovascular Adverse Events.

Hepatorenal syndrome (HRS) is a serious complication of decompensated liver cirrhosis that results in acute kidney injury (AKI). The mortality rate is high. Endothelial dysfunction secondary to liver cirrhosis is a key driver of the development of portal hypertension, which is eventually complicated by ascites and HRS. Ultimately, splanchnic vasodilation and excess gut lymph production result in ascites, low effective arterial blood volume, and maladaptive compensatory mechanisms that contribute to renal hypoperfusion and injury. While the only curative treatment is liver transplantation, vasoconstrictors and albumin have been the mainstay of treatment for candidates who are ineligible or waiting for transplantation. On September 14, 2022, terlipressin, a V1 vasopressin receptor agonist, was approved by the Food and Drug Administration for the treatment of HRS-AKI. In clinical trials, terlipressin plus albumin have been superior to albumin alone and equivocal to noradrenaline plus albumin in renal function improvement. Terlipressin, however, does not improve survival, is costly, and is associated with severe adverse events-including severe cardiac and vascular complications. The aim of this review is to provide an overview of terlipressin pharmacology, adverse events-with a focus on cardiovascular complications-and comparative randomized controlled trials that resulted in the Food and Drug Administration's approval of terlipressin. New literature since its approval and ongoing clinical trials will also be highlighted.

Milvexian: A Focus on a New Oral Anticoagulant that Targets Factor XIa for Thromboembolism Prophylaxis.

Drugs that target factor XI and/or XIa have been evaluated as alternatives to existing anticoagulants, in light of studies that indicate that a decrease in Factor XI/XIa levels or activity may result in a lower risk of thrombosis without a significant increase in bleeding risk. Milvexian is an investigational small-molecule factor XIa inhibitor that has recently completed phase 2 clinical trials. Preclinical studies were suggestive of its potential to prevent arterial and venous thrombosis. It was well-tolerated in healthy participants, as well as in participants with mild or moderate hepatic impairment and moderate or severe renal impairment. Notably, patients who received milvexian after knee arthroplasty had a dose-proportional lower incidence of venous thromboembolism compared to patients who received postoperative enoxaparin, and they had a lower incidence of clinically relevant bleeding. A separate phase 2 trial was conducted that assessed the use of milvexian for secondary stroke prevention in patients who had ischemic stroke or transient ischemic attack. It failed its primary objective of establishing a dose-response relationship between milvexian and a composite endpoint of symptomatic ischemic stroke or covert brain infarction. The trial did, however, show a reduction in the relative risk of symptomatic ischemic stroke across most of the treatment groups receiving various dosages of milvexian compared to placebo. The efficacy of milvexian in secondary stroke prevention will be further assessed in an upcoming phase 3 trial. Additional upcoming phase 3 trials will also assess its efficacy in stroke prevention in patients with atrial fibrillation as well as in event reduction in patients with acute coronary syndrome.

Sacubitril-Valsartan (LCZ696) in the Treatment of Systemic Hypertension: An Updated Review of Neprilysin Inhibition Combined with Angiotensin II Receptor Blockade.

Sacubitril-valsartan (LCZ696) has been demonstrated to be a highly effective treatment for heart failure with preserved ejection fraction since its Food and Drug Administration approval in 2015, and a growing body of evidence suggests its emergence as a hypertensive medication. It acts as an inhibitor of both neprilysin and the renin-angiotensin-aldosterone system, approaching the control of a multi-faceted pathology in multiple unique ways. Because 48% of US adults are affected by hypertension, with less than half of patients achieving controlled blood pressure, and the high correlation between uncontrolled hypertension and cardiovascular mortality, it is crucial to investigate new pharmacotherapies for managing this disease. This review discusses the current evidence of sacubitril-valsartan trials in hypertension management, with a focus on distinct populations and hypertension subsets. Asian populations are predisposed to salt-sensitive hypertension and have been shown to benefit from sacubitril-valsartan more than olmesartan, an angiotensin receptor blocker (ARB). Systolic hypertension from stiff, aging arteries commonly affects individuals over the age of 65 years, and responds demonstrably better to sacubitril-valsartan than ARB monotherapy. Patients with treatment-resistant hypertension, especially those with heart failure, also show significantly improved blood pressure when treated with sacubitril-valsartan over ARBs. We conclude with a discussion of sacubitril-valsartan's potential role in managing noncardiac disease.

The Role of Palliative Care in Cardiovascular Disease.

The American Heart Association has recommended that palliative care be integrated into the care of all patients with advanced cardiac illnesses. Notwithstanding, the number of patients receiving specialist palliative intervention worldwide remains extremely small. This review examines the nature of palliative care and what is known about its delivery to patients with cardiac illness. Most of the published literature on the subject concern advanced heart failure; however, some data also exist regarding patients with heart transplantation, pulmonary hypertension, valvular disease, congenital heart disease, indwelling devices, mechanical circulatory support, and advanced coronary disease. In addition, outcome data, certification requirements, workforce challenges, barriers to implementation, and a potential caveat about palliative care will also be examined. Further work is required regarding appropriate means of implementation, quality control, and timing of intervention.

Cardiopulmonary Resuscitation Education in United States Schools: Shortcomings and Future Directions.

Cardiopulmonary resuscitation (CPR) is a lifesaving procedure that is performed during a cardiac arrest. CPR consists of chest compressions, rescue breaths, and the usage of an automated external defibrillator (AED) based on availability. Performance of CPR can greatly increase the chances of survival by enabling the manual perfusion of vital organs in lieu of the heart's normal function. Despite extensive studies demonstrating the efficacy and necessity of CPR in an emergency, most of the public across the United States is ill-equipped and/or educated on how to perform it. While there may be other contributing factors, the lack of CPR education across schools in the United States almost certainly furthers the CPR illiteracy of the general population. Although states require some degree of CPR training, the level of education that students receive varies widely across communities and school districts, largely dictated by the available funding for training courses. Despite the lack of CPR education in the United States, studies conducted abroad have shown the efficacy of a CPR course in preparing students to respond in emergencies-lending hope to mending the current situation in the United States. In this article, we analyze legislation dictating CPR instruction and hypothesize ways in which states' Department of Education might be able to promote education and hands-on experience for students across all ages of schooling. Ultimately, we hope to highlight the importance and feasibility of preparing the next generation of citizens across the United States to respond when their name is called upon in an emergency.

A Personalized Cell-Based Therapy for Ischemic Heart Failure With Reduced Ejection Fraction: Safety and Feasibility Outcomes of the Roll-In Cohort of the CardiAMP Cell Therapy Trial and Review of Similar Trials.

CardiAMP Cell Therapy for Heart Failure trial is a prospective, multicenter, randomized, controlled, double-blinded trial that has been granted breakthrough designation by the United States Food and Drug Administration. This trial evaluates clinical outcomes of intramyocardial delivery of a high dose of autologous bone marrow mononuclear cells in chronic postmyocardial infarction heart failure patients. This trial represents the first attempt to personalize marrow-derived cell-based therapy for the treatment of ischemic heart failure with reduced ejection fraction. The roll-in cohort of 10 patients demonstrated improvements in 6-minute walk distance at 6 months (+47.8 m, P = 0.01), 12 months (+46.4 m, P = 0.06), and 24 months (+31 m), and improvements in New York Heart Association class at 3 months (P = 0.015) and 6 months (P = 0.037). Four patients were reduced to New York Heart Association class I at 24 months and Minnesota Living with Heart Failure Questionnaire score was improved in 6 of 10 patients at 24 months. The improved clinical outcomes demonstrated in CardiAMP are consistent with previous clinical trials including the Transendocardial Autologous Cells in Ischemic Heart Failure (TAC-HFT) trial, Prospective Randomized Trial of Direct Endomyocardial Implantation of Bone Marrow Cells for Treatment of Severe Coronary Artery Diseases (PROTECT-CAD), and REGENERATE-Ischemic Heart Disease trial.