Cardiac Rehabilitation in Patients Acutely Managed for Cardiogenic Shock (ENIGMA) (ENIGMA)

A framEwork for aN InteGrated assessMent of cArdiac Rehabilitation Programs in Patients Acutely Managed for Cardiogenic Shock - ENIGMA-shock

This is a prospective and retrospective multicentre study conducted under the scientific coordination of the IRCCS Fondazione Don Gnocchi and funded by the Italian Ministry of Health (PNRR-MCNT2-2023-12377767). Using the Altshock registry, the largest multicentre Cardiogenic Shock (CS) registry in Italy, which currently has registered more than 1,000 CS patients across Italy, we will recruit patients to: (1) provide a granular assessment of post-acute phase programmes, patients' functional disability, return to work and quality of life, including specific reference to gender; (2) implement specific pathways of care in the post-acute phase; (3) provide a multidimensional assessment, thus validating an innovative model in comparison with the traditional pathway, defining the potential benefits to and impact on economic efficiency and the general sustainability of this therapeutic trajectory.

Study Overview

• Status: Recruiting
• Conditions: Cardiogenic Shock
• Intervention / Treatment: Other: Cardiac Rehabilitation intervention

Detailed Description

Study Population: The study will include all consecutive Cardiogenic Shock (CS) patients from the Altshock registry. The primary outcome is all-cause death and readmission-free survival at 6 months and 1 year post-ICU discharge. Secondary outcomes include functional recovery measured by illness severity (using the Medical Research Council Scale and electromyography if needed), disease-specific PROM (Kansas City Cardiomyopathy Questionnaire), and a chronic condition PROM (Long-Term Conditions Questionnaire) at 6 months.

Sample Size: An estimated cohort of 2000 CS patients, with around 1240 survivors, will be studied. This sample allows us to detect a 10% difference in death and readmission-free survival rates between those receiving post-acute care services and those who do not, with 80% power and a 5% significance level.

Validation and Assessment: A mixed-method approach will validate the innovative care model, incorporating clinical data, health economics, and professional perceptions. Key performance indicators and a RACI matrix will guide the implementation, with a focus on short- and long-term organizational impacts, economic benefits, and healthcare professional perceptions.

Data Analysis: Quantitative variables will be analyzed using standard statistical methods, and survival analysis will compare groups using Kaplan-Meier curves and log-rank tests. Multivariable Cox models will assess the impact of post-acute care services on outcomes. Economic analyses will involve cost-effectiveness and budget impact assessments.

Rehabilitation Intervention: Post-acute care, including cardiac and neuromotor rehabilitation, is critical for CS patients to prevent complications and rehospitalization. The rehabilitation program will include respiratory physiotherapy, muscle strengthening, endurance training, cardiovascular exercises, and secondary prevention strategies. Neuromotor rehabilitation will address sarcopenia and polyneuropathies with targeted exercises and advanced technologies like robotics and FES.

Expected Outcomes: The ENIGMA project aims to improve CS patient outcomes by transforming post-acute care, reducing mortality, enhancing quality of life, and proving the cost-effectiveness and sustainability of innovative care pathways.

• Study Type: Observational
• Enrollment (Estimated): 2000

Contacts and Locations

• Study Contact: Name: Nuccia Morici, MD; Phone Number: 00390240308122; Email: nmorici@dongnocchi.it
• Study Contact Backup: Name: Paolo Pedersini, MSc; Phone Number: 00390307245005; Email: ppedersini@dongnocchi.it

Study Locations

• Italy
  • Milan, Italy, 20148
    • Recruiting
    • Fondazione Don Gnocchi
    • Contact: Nuccia Morici, MD; Phone Number: 0039 02 40308519; Email: nmorici@dongnocchi.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Probability Sample

Study Population

All consecutive patients with Cardiogenic Shock (CS) will be included. The deferred consent is admitted for non-competent patients.

Description

Inclusion Criteria:

• All consecutive patients with a clinical diagnosis of Cardiogenic Shock.

Exclusion Criteria:

• Refusal to give informed consent.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Cardiogenic Shock; Study population: All consecutive patients with a clinical diagnosis of Cardiogenic Shock enrolled in the Altshock registry will be included.

Other: Cardiac Rehabilitation intervention; The cardiac rehabilitation program for post-CS patients includes respiratory physiotherapy, muscle strengthening and endurance training such as walking, treadmill exercises, and cycling, all tailored to the patient's capabilities. Cardiovascular training involves interval and continuous aerobic exercises to improve heart function. The program emphasizes secondary prevention strategies, including lifestyle changes and medication management. Neuromotor rehabilitation addresses sarcopenia and polyneuropathies through targeted exercises like balance training, gait retraining, and the use of advanced technologies like functional electrical stimulation (FES), robotic devices, and virtual/augmented reality. Cognitive-behavioral therapy (CBT) helps manage the psychological effects of severe cardiovascular events. The program also includes speech and occupational therapy, planning for home reintegration, and telerehabilitation to ensure long-term recovery.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-cause of death	Incidence of all-cause death	1 Year
Readmission in hospital for any cause	Incidence of readmission	1 Year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Severity of critical illness polyneuropathy	Assessment using clinical evaluation (using the Medical Research Council Scale for Muscle Strength), with electromyography and nerve conduction if required	6-months
Disease-specific PROM	The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a specialized tool designed to assess the health-related quality of life in patients with heart failure. It measures the physical, social, and emotional impacts of heart failure, providing insights into the effectiveness of treatments and guiding clinical decisions.	6-Months
Chronic-condition PROM	standardized by the Food and Drug Administration and the Oxford Patient-Reported Outcomes Group's Long-Term Conditions Questionnaire	6-months
PREMS: patient's opinion regarding their clinical service.	Patients will be questioned about the clinical service received. The items explored will be coordination and integration of care; information, communication, and education; physical comfort; emotional support; welcoming and involvement of family and friends; transition and continuity; and access to care. Patients will define every item in terms of low quality, moderate quality and high quality.	6-months

Collaborators and Investigators

• Sponsor: Fondazione Don Carlo Gnocchi Onlus
• Collaborators: Azienda Ospedaliera Brotzu; Azienda Ospedaliera OO.RR. S. Giovanni di Dio e Ruggi D'Aragona; Ospedale Civile Ss. Antonio e Biagio e Cesare Arrigo, Alessandria, Italy; ASST Grande Ospedale Metropolitano Niguarda, Milano, Italy

Publications and helpful links

General Publications

• Anderson L, Oldridge N, Thompson DR, Zwisler AD, Rees K, Martin N, Taylor RS. Exercise-Based Cardiac Rehabilitation for Coronary Heart Disease: Cochrane Systematic Review and Meta-Analysis. J Am Coll Cardiol. 2016 Jan 5;67(1):1-12. doi: 10.1016/j.jacc.2015.10.044.
• Yang T, Li Z, Jiang L, Wang Y, Xi X. Risk factors for intensive care unit-acquired weakness: A systematic review and meta-analysis. Acta Neurol Scand. 2018 Aug;138(2):104-114. doi: 10.1111/ane.12964. Epub 2018 May 29.
• van Diepen S, Katz JN, Albert NM, Henry TD, Jacobs AK, Kapur NK, Kilic A, Menon V, Ohman EM, Sweitzer NK, Thiele H, Washam JB, Cohen MG; American Heart Association Council on Clinical Cardiology; Council on Cardiovascular and Stroke Nursing; Council on Quality of Care and Outcomes Research; and Mission: Lifeline. Contemporary Management of Cardiogenic Shock: A Scientific Statement From the American Heart Association. Circulation. 2017 Oct 17;136(16):e232-e268. doi: 10.1161/CIR.0000000000000525. Epub 2017 Sep 18.
• Rab T, Ratanapo S, Kern KB, Basir MB, McDaniel M, Meraj P, King SB 3rd, O'Neill W. Cardiac Shock Care Centers: JACC Review Topic of the Week. J Am Coll Cardiol. 2018 Oct 16;72(16):1972-1980. doi: 10.1016/j.jacc.2018.07.074. Erratum In: J Am Coll Cardiol. 2018 Nov 27;72(21):2685. doi: 10.1016/j.jacc.2018.10.028.
• Kapur NK, Kanwar M, Sinha SS, Thayer KL, Garan AR, Hernandez-Montfort J, Zhang Y, Li B, Baca P, Dieng F, Harwani NM, Abraham J, Hickey G, Nathan S, Wencker D, Hall S, Schwartzman A, Khalife W, Li S, Mahr C, Kim JH, Vorovich E, Whitehead EH, Blumer V, Burkhoff D. Criteria for Defining Stages of Cardiogenic Shock Severity. J Am Coll Cardiol. 2022 Jul 19;80(3):185-198. doi: 10.1016/j.jacc.2022.04.049.
• Mueller S, Winzer EB, Duvinage A, Gevaert AB, Edelmann F, Haller B, Pieske-Kraigher E, Beckers P, Bobenko A, Hommel J, Van de Heyning CM, Esefeld K, von Korn P, Christle JW, Haykowsky MJ, Linke A, Wisloff U, Adams V, Pieske B, van Craenenbroeck EM, Halle M; OptimEx-Clin Study Group. Effect of High-Intensity Interval Training, Moderate Continuous Training, or Guideline-Based Physical Activity Advice on Peak Oxygen Consumption in Patients With Heart Failure With Preserved Ejection Fraction: A Randomized Clinical Trial. JAMA. 2021 Feb 9;325(6):542-551. doi: 10.1001/jama.2020.26812.
• Molloy C, Long L, Mordi IR, Bridges C, Sagar VA, Davies EJ, Coats AJ, Dalal H, Rees K, Singh SJ, Taylor RS. Exercise-based cardiac rehabilitation for adults with heart failure. Cochrane Database Syst Rev. 2024 Mar 7;3(3):CD003331. doi: 10.1002/14651858.CD003331.pub6.
• Balady GJ, Ades PA, Bittner VA, Franklin BA, Gordon NF, Thomas RJ, Tomaselli GF, Yancy CW; American Heart Association Science Advisory and Coordinating Committee. Referral, enrollment, and delivery of cardiac rehabilitation/secondary prevention programs at clinical centers and beyond: a presidential advisory from the American Heart Association. Circulation. 2011 Dec 20;124(25):2951-60. doi: 10.1161/CIR.0b013e31823b21e2. Epub 2011 Nov 14. No abstract available.
• Lavie CJ, Ozemek C, Carbone S, Katzmarzyk PT, Blair SN. Sedentary Behavior, Exercise, and Cardiovascular Health. Circ Res. 2019 Mar;124(5):799-815. doi: 10.1161/CIRCRESAHA.118.312669.
• Aburub A, Darabseh MZ, Badran R, Shurrab AM, Amro A, Degens H. The Application of Robotics in Cardiac Rehabilitation: A Systematic Review. Medicina (Kaunas). 2024 Jul 18;60(7):1161. doi: 10.3390/medicina60071161.
• Luscher TF, Thiele H. Cardiogenic shock: do we need a paradigm shift? Eur Heart J. 2024 Oct 14;45(39):4178-4180. doi: 10.1093/eurheartj/ehae425. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): August 31, 2024
• Primary Completion (Estimated): March 31, 2026
• Study Completion (Estimated): August 31, 2026

Study Registration Dates

• First Submitted: August 21, 2024
• First Submitted That Met QC Criteria: August 23, 2024
• First Posted (Actual): August 27, 2024

Study Record Updates

• Last Update Posted (Actual): October 29, 2024
• Last Update Submitted That Met QC Criteria: October 25, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Rehabilitation; Cardiogenic Shock
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Infarction; Necrosis; Myocardial Ischemia; Myocardial Infarction; Ischemia; Shock, Cardiogenic; Shock
• Other Study ID Numbers: ENIGMA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No