Early Utilization of Mechanical Circulatory Support in Acute Myocardial Infarction Complicated by Cardiogenic Shock: The National Cardiogenic Shock Initiative.

BACKGROUND: Acute myocardial infarction complicated by cardiogenic shock (AMI-CS) is associated with significant morbidity and mortality. Mechanical circulatory support (MCS) devices increase systemic blood pressure and end organ perfusion while reducing cardiac filling pressures. METHODS AND RESULTS: The National Cardiogenic Shock Initiative (NCT03677180) is a single-arm, multicenter study. The purpose of this study was to assess the feasibility and effectiveness of utilizing early MCS with Impella in patients presenting with AMI-CS. The primary end point was in-hospital mortality. A total of 406 patients were enrolled at 80 sites between 2016 and 2020. Average age was 64±12 years, 24% were female, 17% had a witnessed out-of-hospital cardiac arrest, 27% had in-hospital cardiac arrest, and 9% were under active cardiopulmonary resuscitation during MCS implantation. Patients presented with a mean systolic blood pressure of 77.2±19.2 mm Hg, 85% of patients were on vasopressors or inotropes, mean lactate was 4.8±3.9 mmol/L and cardiac power output was 0.67±0.29 watts. At 24 hours, mean systolic blood pressure improved to 103.9±17.8 mm Hg, lactate to 2.7±2.8 mmol/L, and cardiac power output to 1.0±1.3 watts. Procedural survival, survival to discharge, survival to 30 days, and survival to 1 year were 99%, 71%, 68%, and 53%, respectively. CONCLUSIONS: Early use of MCS in AMI-CS is feasible across varying health care settings and resulted in improvements to early hemodynamics and perfusion. Survival rates to hospital discharge were high. Given the encouraging results from our analysis, randomized clinical trials are warranted to assess the role of utilizing early MCS, using a standardized, multidisciplinary approach.

The ARF GAPs ELMOD1 and ELMOD3 act at the Golgi and cilia to regulate ciliogenesis and ciliary protein traffic.

ELMODs are a family of three mammalian paralogues that display GTPase-activating protein (GAP) activity toward a uniquely broad array of ADP-ribosylation factor (ARF) family GTPases that includes ARF-like (ARL) proteins. ELMODs are ubiquitously expressed in mammalian tissues, highly conserved across eukaryotes, and ancient in origin, being present in the last eukaryotic common ancestor. We described functions of ELMOD2 in immortalized mouse embryonic fibroblasts (MEFs) in the regulation of cell division, microtubules, ciliogenesis, and mitochondrial fusion. Here, using similar strategies with the paralogues ELMOD1 and ELMOD3, we identify novel functions and locations of these cell regulators and compare them to those of ELMOD2, allowing the determination of functional redundancy among the family members. We found strong similarities in phenotypes resulting from deletion of either Elmod1 or Elmod3 and marked differences from those arising in Elmod2 deletion lines. Deletion of either Elmod1 or Elmod3 results in the decreased ability of cells to form primary cilia, loss of a subset of proteins from cilia, and accumulation of some ciliary proteins at the Golgi, predicted to result from compromised traffic from the Golgi to cilia. These phenotypes are reversed upon activating mutant expression of either ARL3 or ARL16, linking their roles to ELMOD1/3 actions.

Hot topics in interventional cardiology: Proceedings from the society for cardiovascular angiography and interventions (SCAI) 2021 think tank.

The Society for Cardiovascular Angiography and Interventions (SCAI) Think Tank is a collaborative venture that brings together interventional cardiologists, administrative partners, and select members of the cardiovascular industry community annually for high-level field-wide discussions. The 2021 Think Tank was organized into four parallel sessions reflective of the field of interventional cardiology: (a) coronary intervention, (b) endovascular medicine, (c) structural heart disease, and (d) congenital heart disease. Each session was moderated by a senior content expert and co-moderated by a member of SCAI's Emerging Leader Mentorship program. This document presents the proceedings to the wider cardiovascular community in order to enhance participation in this discussion, create additional dialog from a broader base, and thereby aid SCAI, the industry community and external stakeholders in developing specific action items to move these areas forward.

Basic surface electrocardiogram interpretation for the pharmacist.

PURPOSE: The electrocardiogram (ECG) is an invaluable tool for clinicians that provides important information about a patient's heart. As clinical pharmacists play an ever-increasing role in cardiovascular care, ECG interpretation is an important skill with which to become familiar. SUMMARY: The ECG provides information on both electrical and biomechanical aspects of the heart. Electrical information such as the rhythm, rate, and axis of the electrical activity can all be provided by the ECG. Biomechanical information about the heart, such as the presence of ventricular hypertrophy and repolarization changes that may be associated with ischemia or myocardial injury, can also easily be gleaned from the ECG. Furthermore, the ECG plays a central role in both the diagnosis and treatment of common clinical conditions such as atrial fibrillation, ischemic heart disease, and QT interval prolongation. CONCLUSION: The ECG is one of the most commonly performed diagnostic tests, and clinicians should become familiar with its basic interpretation.

Cost savings for pVAD compared to ECMO in the management of acute myocardial infarction complicated by cardiogenic shock: An episode-of-care analysis.

BACKGROUND: Acute myocardial infarction complicated by cardiogenic shock (AMICS) occurs in up to 10% of acute myocardial infarction admissions and is associated with high mortality, frequent adverse outcomes, prolonged hospitalizations, extensive medical resource utilization, and major cost. Using hospital cost data for Medicare Fee-for-Service (FFS) patients with AMICS, we sought to evaluate in hospital and 45-day outcomes and cost, comparing patients treated with percutaneous ventricular assist device (pVAD) versus extracorporeal membrane oxygenation (ECMO). The goal of this study was to better understand clinical and economic outcomes of AMICS to help clinicians and hospitals optimize outcomes most economically for AMICS patients. METHODS: A retrospective claims analysis identified patients from the full census Medicare Standard Analytic Files compiled by the Center for Medicare and Medicaid (CMS) including: Inpatient, Outpatient, Skilled Nursing Facility and Home Health files for Medicare FFS beneficiaries. Study costs were defined as the total costs incurred by providers for treating a population with AMICS. Medicare FFS beneficiaries who experienced an inpatient admission during the index period (January 1, 2015 to March 31, 2017) with a diagnosis of AMICS were eligible for study inclusion and were identified by the presence of appropriate International Classification of Diseases, Ninth and Tenth Versions (ICD-9 and ICD-10) diagnosis and procedure codes. To create a matched sample and control for any baseline differences, a 1:1 Propensity Score Matching (PSM) was performed based on criteria such as age, gender, race, geographic distribution, and 11 high-cost comorbidities (e.g., congestive HF, coronary artery disease, diabetes, etc.). Index length of stay (LOS), index costs, discharge disposition (including mortality), post-index utilization, and episode-of-care (EOC) costs were reviewed. EOC was defined as index admission for all patients plus a 45-day post index period for patients who survived the index admission. RESULTS: Each cohort included 338 patients. Index in-hospital mortality rates were 53% for pVAD versus 64% for ECMO (178 vs. 217; p = .0023), and total EOC in-hospital mortality rates were 66% for pVAD versus 74% for ECMO (222 vs. 250; p = .0160). Index LOS for pVAD was 27% lower versus ECMO (12.12 vs. 16.59; p = .0006). The index LOS for patients discharged alive was 25% lower for pVAD versus ECMO (17.73 vs. 23.62; p = .0016). For patients that experienced in-hospital mortality during their index stay, pVAD had a 44% lower LOS compared to ECMO (7.08 vs. 12.66; p < .0001). Following index hospitalization, the average cost savings with additional inpatient care was 31% lower for pVAD patients ($62,188 vs. $90,087; p = NS). During the EOC, pVAD patients incurred 32% lower costs compared to ECMO patients ($117,849 vs. $172,420; <.0001). CONCLUSIONS: This study of Medicare FFS patients demonstrates that hospitals utilizing pVAD for appropriately selected AMICS patients have reduced mortality rates and reduced index LOS with lower index facility costs and lower post index 45-day costs. The study results offer hospitals and clinicians an opportunity to improve clinical outcomes and reduce total EOC costs in treating patients with AMI complicated by CS.

Balloon assisted translocation of the mitral anterior leaflet to prevent left ventricular outflow obstruction (BATMAN): A novel technique for patients undergoing transcatheter mitral valve replacement.

INTRODUCTION: Transcatheter mitral valve replacement (TMVR) is an option for patients at high risk for mitral valve replacement or repair via sternotomy or left thoracotomy approach. TMVR carries up to 22% risk of left ventricular outflow tract (LVOT) obstruction. Severe LVOT obstruction can have devastating hemodynamic and clinical consequences. HYPOTHESIS: We previously presented a novel technique to prevent LVOT obstruction during transapical retrograde mitral valve replacement, by penetrating and ballooning the anterior mitral leaflet (AML), resulting in creation of a "hole" and posterior translocation of AML, then deploying the valve. METHODS: Three patients underwent TMVR at Saint Louis University for severe mitral regurgitation after being deemed too high risk for surgery, and not candidates for a Mitra-clip procedure. These patients were deemed to be at risk for LVOT obstruction based on the preprocedural evaluation. Via transapical approach, a needle was advanced "through," perforating the AML and wire was placed in the left atrium. Over the wire, an 20-mm valvuloplasty balloon was positioned "within" the anterior leaflet and inflated leading to translocation of the AMVL. Then the valve was deployed. RESULTS: This novel technique has been performed on three patients at our institution. Sapien S3 transcatheter valves were used in all three patients, with 100% procedural success rate. Intraoperative TEE demonstrated no significant LVOT obstruction, cardiopulmonary bypass time was 42-44 min. CONCLUSION: The balloon assisted translocation of the mitral anterior leaflet to prevent left ventricular outflow obstruction technique described here may offer the option of transcatheter mitral valve implantation in patients at high risk of LVOT obstruction. A variation of this technique to allow application in cases with transseptal approach is under investigation.

Impella support and acute kidney injury during high-risk percutaneous coronary intervention: The Global cVAD Renal Protection Study.

BACKGROUND: Protection against acute kidney injury (AKI) has been reported with the use of Impella during high-risk percutaneous coronary intervention (HR-PCI). We sought to evaluate this finding by determining the occurrence of AKI during Impella-supported HR-PCI in patients from the Global cVAD Study and compare this incidence with their calculated AKI risk at baseline. METHODS AND RESULTS: In this prospective, multicenter study, we enrolled 314 consecutive patients. We included 223 patients that underwent nonemergent HR-PCI supported with Impella 2.5 or Impella CP and excluded those requiring hemodialysis prior to HR-PCI (19) and those with insufficient data (72). The primary outcome was AKI postprocedurally at 48 hr versus the predicted risk of AKI according to Mehran risk score. Logistic regression analysis determined predictors of AKI. Overall, 4.9% (11) of Impella-supported patients developed AKI (exclusively stage 1) at 48 hr versus a predicted rate of 21.9%, representing a 77.6% lower AKI rate (p < .0001). In this study, no Impella-supported patients required renal replacement therapy. Estimated glomerular filtration rate (ml/min/1.73 m2 ) alone predicted AKI (adjusted odds ratio [AOR]: 4.915; 95% confidence intervals [CI]: 1.02-23.53, p = .046), and increasing contrast had insignificant effects on AKI during high-risk PCI (AOR: 1.15; 95% CI: 0.87-1.51, p = .332). In patients not protected from AKI, the postprocedure incidence of AKI was not significantly greater and did not correlate with chronic kidney disease severity. CONCLUSION: The incidence of AKI was lower during HR-PCI than expected from current risk models. Although further exploration of this finding is warranted, these data support a new protective strategy against AKI during HR-PCI.

Leadless solution for arrhythmia-related sudden unexpected death in epilepsy.

A leadless pacemaker is a recently approved pacing technology that helps mitigate lead-related complications, but it has several limitations. Careful candidate selection is needed. Here, we demonstrate leadless pacing as the solution for prolonged postictal bradycardia/asystole; there is no consensus regarding pacemaker implantation for seizure patients with such a risk of sudden cardiac death.

Carbon Dioxide Exposure Resulting From Hood Protective Equipment Used in Joint Arthroplasty Surgery.

BACKGROUND: To protect both the surgeon and patient during procedures, hooded protection shields are used during joint arthroplasty procedures. Headache, malaise, and dizziness, consistent with increased carbon dioxide (CO2) exposure, have been anecdotally reported by surgeons using hoods. We hypothesized that increased CO2 concentrations were causing reported symptoms. METHODS: Six healthy subjects (4 men) donned hooded protection, fan at the highest setting. Arm cycle ergometry at workloads of 12 and 25 watts (W) simulated workloads encountered during arthroplasty. Inspired O2 and CO2 concentrations at the nares were continuously measured at rest, 12 W, and 25 W. At each activity level, the fan was deactivated and the times for CO2 to reach 0.5% and 1.0% were measured. RESULTS: At rest, inspired CO2 was 0.14% ± 0.04%. Exercise had significant effect on CO2 compared with rest (0.26% ± 0.08% at 12 W, P = .04; 0.31% ± 0.05% at 25 W, P = .003). Inspired CO2 concentration increased rapidly with fan deactivation, with the time for CO2 to increase to 0.5% and 1.0% after fan deactivation being rapid but variable (0.5%, 12 ± 9 seconds; 1%, 26 ± 15 seconds). Time for CO2 to return below 0.5% after fan reactivation was 20 ± 37 seconds. CONCLUSION: During simulated joint arthroplasty, CO2 remained within Occupational Safety and Health Administration (OSHA) standards with the fan at the highest setting. With fan deactivation, CO2 concentration rapidly exceeds OSHA standards.

Fresh osteochondral allograft transplantation for osteochondritis dissecans of the capitellum in baseball players.

BACKGROUND: Osteochondritis dissecans (OCD) of the capitellum is a rare yet debilitating injury seen in young athletes. This is the first report in the literature describing fresh osteochondral allograft transplantation (FOCAT) to treat OCD of the capitellum. METHODS: Nine male baseball players (mean age, 15.3; range, 14-18 years), with OCD of the capitellum were treated with FOCAT. There were 6 pitchers and 3 position players. A ligament-sparing, mini-open approach was used. A fresh femoral hemicondyle was used as a donor source. Of the 9 patients, 7 required 1 plug and 2 required 2 plugs. The average plug diameter was 11 mm (range, 8-18 mm). Five plugs were press fit, and 4 required additional fixation. Clinical outcomes were evaluated at a mean follow-up of 48.4 months (range, 11-90 months). Preoperative and postoperative outcome scores were calculated using the paired t test. RESULTS: The Mayo Elbow Performance score improved from an average 57.8 to 98.9 (P < .01). The Oxford Elbow Score improved from 22.4 to 44.8 (P < .01). The Disabilities of the Arm, Shoulder and Hand score improved from 35.2 to 5.4 (P < .01). The visual analog scale score improved from 7.8 to 0.5 (P < .01). The Kerlan-Jobe Orthopaedic Clinic Shoulder and Elbow score improved from 32.6 to 82.5 (P < .01). All patients returned to throwing and were still active in their sport or played at least 2 years of baseball before leaving the sport unrelated to the elbow. CONCLUSIONS: FOCAT for OCD of the capitellum in properly selected cases is a viable treatment with significant functional improvement and pain reduction in throwers.

Use of a Vascular Sheath in the Axillary Artery as an Alternative Access Approach for Placing an Impella 5.0 Device.

Many patients who are in cardiogenic shock need mechanical support for clinical stabilization after acute insults such as myocardial infarction. However, the placement of advanced devices can be hindered by anatomic constraints or the physiologic sequelae of shock, as we describe in this report. A 67-year-old woman with prior coronary artery bypass grafting and extensive chest-wall scarring from previous defibrillator implantations presented with myocardial infarction and refractory cardiogenic shock. The patient's vascular anatomy and prior surgery precluded conventional percutaneous implantation of an Impella 5.0 ventricular support device. We delivered the Impella device through the patient's tortuous, vasoconstricted axillary artery with use of a vascular sheath and other percutaneous techniques. The success of this approach suggests that combining the expertise of cardiologists and cardiovascular surgeons can improve the outcomes of patients with complex anatomic issues.

Pooled comparison of regadenoson versus adenosine for measuring fractional flow reserve and coronary flow in the catheterization laboratory.

BACKGROUND: Adenosine is the gold standard for augmenting coronary flow during fractional flow reserve (FFR) testing of intermediate coronary stenoses. However, intravenous infusion is time-consuming and intracoronary injection is subject to variability. Regadenoson is a newer adenosine alternative administered as a single intravenous bolus during nuclear stress testing, but its efficacy and safety during FFR testing have been evaluated only in small, single-center studies. METHODS: We pooled data from 5 academic hospitals, in which patients undergoing clinically-indicated FFR prospectively underwent comparison of intravenous adenosine infusion (140-175mcg/kg/min) versus regadenoson bolus (400mcg). Hemodynamics and symptoms with adenosine were recorded until maximal hyperemia occurred, and after returning to baseline hemodynamics, regadenoson was administered and monitoring was repeated. In a subset of patients with coronary flow data, average peak velocity (APV) at the distal flow sensor was recorded. RESULTS: Of 149 patients enrolled, mean age was 59±9years, 76% were male, and 54% underwent testing of the left anterior descending artery. Mean adenosine-FFR and regadenoson-FFR were identical (0.82±0.10) with excellent correlation of individual values (r=0.96, p<0.001) and no difference in patient-reported symptoms. Four patients (2.6%) had discrepancies between the 2 drugs for the clinical decision-making cutoff of FFR≤0.80. Coronary flow responses to adenosine and regadenoson were similar (APV at maximal hyperemia 36cm/s for both, p=0.81). CONCLUSIONS: Regadenoson single-bolus administration has comparable FFR, symptoms, and coronary flow augmentation when compared with standard intravenous adenosine infusion. With its greater ease of administration, regadenoson may be a more "user-friendly" option for invasive ischemic testing.

Beyond warfarin: a patient-centered approach to selecting novel oral anticoagulants for stroke prevention in atrial fibrillation.

BACKGROUND: Warfarin reduces stroke in patients with atrial fibrillation. However, its narrow therapeutic index and need for chronic monitoring are barriers to its optimal utilization in many patients. The recent introduction of 3 novel oral anticoagulants (NOACs), as alternatives to warfarin, may change the eligibility and management of patients with nonvalvular atrial fibrillation (NVAF) who require systemic anticoagulation. PURPOSE: To summarize contemporary indications for anticoagulation in NVAF, and to help provide patient-centered clinical decision making for selecting warfarin or 1 of the NOACs (dabigatran, rivaroxaban, apixaban) based on randomized trials and mechanistic data for each drug. DATA SOURCES AND STUDY SELECTION: The primary clinical outcome trials of warfarin and the NOACs, pharmacologic studies, and briefing documents from the US Food and Drug Administration were reviewed. DATA EXTRACTION AND DATA SYNTHESIS: In randomized trials, NOACs were consistently noninferior to warfarin for reducing stroke or systemic embolism in patients with NVAF, with reductions in intracranial bleeding as well. However, NOACs have several important drug-drug interactions, exclusion criteria for specific patient subgroups (eg, severe renal disease), and each medication may have a different impact on other clinical outcomes such as myocardial infarction or gastrointestinal bleeding. Benefits of the new drugs are particularly pronounced when international normalized ratio levels on warfarin are labile. CONCLUSIONS: Warfarin continues to play an important role in the prevention of stroke or systemic embolism in NVAF. Among selected patients, the use of NOACs provides equal or superior benefit, without the need for chronic anticoagulation monitoring or ongoing dose titration.

Comparison of in-hospital outcomes for beta-blocker use versus non-beta blocker use in patients presenting with cocaine-associated chest pain.

Beta blockers are indicated for management of acute coronary syndromes, but they generally are withheld in patients with cocaine-associated chest pain because of concerns for adverse outcomes related to the unique physiological effects of cocaine. Because few clinical studies have evaluated this interaction, we identified patients with toxicology screen results positive for cocaine treated for chest pain at 2 academic hospitals. Clinical characteristics and in-hospital outcomes were compared between patients with and without ß-blocker therapy. We then constructed propensity scores to evaluate the independent relation between ß-blocker use and the composite primary end point of myocardial infarction, stroke, ventricular arrhythmia, or all-cause mortality after adjusting for clinical characteristics. Of 376 consecutive patients with cocaine-related chest pain, ß blockers were used in 164 (44%). Compared with no ß blockers, patients treated with ß blockers were more likely to describe anginal chest pain, to have known cardiovascular risk factors, and to receive other antiatherosclerotic therapies. Despite these higher risk clinical characteristics, patients treated with ß blockers experienced similar peak troponin levels, individual adverse events, and rates of the composite primary end point (15.9% vs 12.3%, p = 0.32). The primary end point also was similar after propensity score analysis (odds ratio 1.37, 95% confidence interval 0.64 to 2.93, p = 0.42), including specific comparisons of beta-1 selective (odds ratio 1.83, 95% confidence interval 0.79 to 4.24) and nonselective (odds ratio 0.90, 95% confidence interval 0.33 to 2.42) ß blockers, when compared with patients not receiving ß blockers. In conclusion, no differences in outcomes were observed between patients treated versus not treated with ß-blocker therapy in the setting of cocaine-related chest pain.

Estimating the adoption of transcatheter aortic valve replacement by US interventional cardiologists and clinical trialists.

BACKGROUND: Despite extensive attention dedicated to transcatheter aortic valve replacement (TAVR) in both the medical literature and lay press, little is known about the anticipated utilization of TAVR by the US cardiology community. HYPOTHESIS: TAVR use is likely to outstrip its initial clinical indications. METHODS: Four days after approval of the first TAVR device in November 2011 by the US Food and Drug Administration, we emailed an online questionnaire to 201 authors of major TAVR clinical trials (trialists) and 461 recent members of an interventional cardiology professional society (clinicians). Responses were compared using χ(2) , t tests, and analysis of variance. RESULTS: Of 205 surveys received (response rate 31%; 114 clinicians, 91 trialists), the majority of respondents were interventionalists (86%) working in academic practices (72%). Although most physicians anticipated referring <25% of their patients with severe aortic stenosis for TAVR, 68% believed that TAVR is equally efficacious as open-heart surgery, and 11% believed that moderate-surgical risk patients should also be considered for TAVR. More clinicians (98%) than trialists (81%) expected to routinely refer patients for TAVR (P < 0.001). Furthermore, the clinicians were anticipating less operator training and lower annual volume requirements for performing TAVR, when compared with the trialists (P ≤ 0.001). CONCLUSIONS: Our findings suggest optimism for TAVR acceptance in the United States., with more conservative expectations regarding training, procedural volume requirements, and anticipated referral patterns among TAVR trialists than clinical interventionalists.

Modern cardiac rehabilitation: Integrating the best measures to reduce a second cardiac event.

Patients with established cardiovascular disease are at high risk for future myocardial infarction, stroke, and death. Interventions that may reduce recurrent cardiovascular events serve a critical role in improving both long-term morbidity and mortality. Cardiac rehabilitation following a cardiac event has been modernized with the integration of coronary risk factor reduction programs in addition to its traditional role of early graded mobilization of the patient and has been shown to significantly benefit men and women with coronary heart disease.

Coronary angiography is the gold standard for patients with significant left ventricular dysfunction.

Left ventricular (LV) dysfunction has been shown to be significantly related to ongoing myocardial ischemia, hibernation, and thus, coronary artery disease. Current treatments for patients with LV dysfunction and concomitant coronary artery disease center around the potential benefit of coronary revascularization, in the form of either coronary artery bypass grafting surgery (CABG) or percutaneous coronary intervention (PCI). Given the great diversity in the patient population making up those with LV dysfunction and coronary artery disease, intense interest has been directed in determining which patients benefit the most from revascularization. Multiple noninvasive evaluations have been utilized in order to select or stratify these patients. However, the gold standard by which clinicians make revascularization determinations is invasive coronary angiography. Within this review, we compare and contrast the noninvasive modalities available to the present day clinician with invasive angiography. Furthermore, we outline the ways in which invasive angiography has been utilized in patients with LV dysfunction and summarize the present guidelines regarding its usefulness.

Potential for Infra-Nodal Heart Block and Cardiogenic Shock With Propofol Administration.

We report a case of infra-nodal complete heart block and cardiogenic shock in a previously healthy 64-year-old man after administration of 180 mg of intravenous Propofol. Although bradycardia, hypotension, and heart block are commonly seen with propofol administration, such findings are transient and respond quickly to administration of vagolytic or sympathomimetic agents suggesting an AV nodal mechanism of heart block. Sustained left ventricular systolic dysfunction and cardiogenic shock by an alternative, non-autonomic mechanism has also been described in the setting of Propofol administration. Our case is the first to note sustained complete infra-nodal heart block in this setting. Early recognition of such a complication, restoration of atrio-ventricular (A-V) synchrony with dual chamber pacing, and aggressive circulatory support is essential in bridging such patients to recovery.