Image

About NPAC Study

Study Hypothesis

Developing a protocol for managing pregnant women with heart disease in India, based on systematically collected prospective data across our nation, and developing a indigenous risk stratification tool and implementing them in day to day management

may

Change the practice patterns in care of women with heart disease & thus improve the maternal and fetal outcome in India.

Primary Objective

  • Develop, implement and evaluate an evidence-based cardio-obstetric care protocol in improving outcomes of PWWHD in India.

Secondary Objectives

  • Develop and validate a risk stratification tool for PWWHD in India
  • Test the applicability of existing risk scores for Indian population (mWHO, CARPREG II, ZAHARA, DEVI)

Methodology (Multimethod study)

  • Cohort model to develop risk stratification tools
  • DELPHI method for stakeholder engagement for development of consensus on intervention (Protocolized Cardio-obstetric care - PCO Care)
  • Quantitative and qualitative process evaluation of implementation of interventions and intermediate outcomes.
  • Cluster randomized controlled trial (Protocolized cardio-obstetric care Vs enhanced usual care.) to evaluate the effectiveness of the intervention model

All consecutive pregnant women with known or newly detected heart diseases mentioned below, seeking antenatal care in the participating sites are eligible for inclusion.

Inclusion Criteria:

  • Structural Heart disease- congenital or acquired
  • Arrhythmic heart disease
  • Ischemic heart disease
  • Aortic diseases
  • Pulmonary vascular disease

Patients with hypertensive disorders of pregnancy or gestational diabetes mellitus without any of the above inclusion criteria – are not eligible.

Time allowed for enrolment in study

  • Antenatal Period
  • Postnatal period up to 2 weeks
  • Postnatal period up to 5 months (Peripartum CMP only)

Exclusion Criteria:

  • Patients with trivial and mild physiological valve lesions
  • Patients below the age of 18
  • Patients who are not able to or not willing to give informed consent.
  • Patients who are part of another intervention trial

Study Phases – GANTT Chart Simplified

  • Observational Phase (1st -18th months)
  • Protocol development Phase (6th to 18th months)
  • Implementation phase (18th – 42nd months)

Objective 1:

(i)Assessing Practice Patterns

Enrollment and Initial Evaluation:

  • Pregnant women with confirmed heart disease
  • Written informed consent in vernacular language
  • Detailed history, clinical, and echocardiographic evaluation
  • Data documented in offline CRF booklet and electronic tool

Antenatal Care and Follow-up:

  • Active follow-up throughout antenatal period.
  • Documentation of antenatal, intra-natal, and postnatal data.
  • Contraceptive advice given

Data Collection:

  • Trained research staff using structured tool
  • Data processed and stored in validated database
  • Periodic audits for data quality

Study Variables Collected

  • 1. Identification: Name, age, contact details, unique ID
  • 2.Background: Socioeconomic status, education, healthcare access, parity
  • 3. CV Health: Suboptimal CV health, substance abuse
  • 4. Clinical Examination: Vital signs, pedal edema, cardiac murmur, rales
  • 5. Biochemical: Hb, RBS, Urea, Creatinine
  • 6. Counselling: Preconception, post-conception, post-delivery details
  • 7. Prior Pregnancy: Earlier pregnancy details, adverse outcomes
  • 8. Cardiac Ailment: History of heart disease, medications, interventions
  • 9. Present Pregnancy: Antenatal details, NYHA status, symptoms
  • 10. Risk Assessment: mWHO, CARPREG II, M-PAC, ZAHARA, DEVI scores
  • 11. Cardiac Medications: Past and present medications
  • 12. ECG: Cardiac rhythm, arrhythmia
  • 13. ECHO: Cardiac lesion, ventricular function, valvular issues
  • 14. Ultrasound: Abdomen features
  • 15. Cardiac Medications: Beta-blocker, anticoagulant, bromocriptine use
  • 16. Contraception: Type used before and after pregnancy
  • 17. Process of Care: Screening, antenatal detection, counselling, medications, interventions, referral

Survey of Cardio-Obstetric Care Process

  • Human resources and infrastructure availability
  • Process of care for PWWHD management
  • In-depth interviews with stakeholders

Protocol Development (6-19 months)

  • Brainstorming sessions (6-9 months): Online and in-person sessions with experts to identify challenges and solutions for protocol-based care.
  • Delphi Panel (10-15 months): Online survey to reach consensus on protocol components and criteria.
  • Protocol writing phase (9-19 months): Authors write sections, central coordinating group completes protocol, and editor group finalizes it.

Protocol Implementation (Parallel Group Cluster RCT)

  • 44 units in India will be randomly assigned to either protocolized cardio-obstetric care (intervention arm) or standard of care (control arm).
  • Patient eligibility: Adult pregnant women with heart disease.
  • Randomization: Computer-generated random numbers, 1:1 allocation ratio.
  • Implementation Arms:
    • Enhanced Usual Care Arm: Treating physicians provide care as per usual practice patterns.
    • PCO Care Arm: Physicians implement care as per the protocol.
  • Adherence Assessment: Optimal (80%), Partial (30-80%), or No adherence (<30%).
  • Duration of treatment and follow-up: Rolling recruitment over 1 year, follow-up until 6 weeks after termination of pregnancy, and telephonic follow-up till 6 months after.

Measurements

  1. All measurements from phase 1 will be included.
  2. Additional process indicators will be added after finalizing the PCO care protocol.

Primary Composite Outcome (Any one of the following)

  • Maternal death (Within 42 days)
  • Resuscitated cardiac arrest
  • New or worsening maternal heart failure requiring treatment escalation or hospitalization
  • New onset or recurrent sustained cardiac arrhythmia requiring treatment
  • Cerebrovascular accident / Stroke
  • Systemic thromboembolism
  • Venous thromboembolism (Deep Vein Thrombosis / Pulmonary Embolism / Invictus trial)
  • Prosthetic valve thrombosis
  • Hemorrhagic complications (Major or minor bleed as per ISTH Criteria)
  • Infective endocarditis
  • Aortic dissection during pregnancy (if applicable)
  • Acute coronary syndrome / Spontaneous Coronary Artery Dissection (SCAD)
  • Urgent cardiac intervention up to the 6th postpartum week (e.g., PTMC for severe symptomatic MS, RF ablation, pericardiocentesis, etc.)

Secondary Outcomes

Maternal Cardiac Outcome

  • Decline in NYHA functional class ≥ 2 during pregnancy
  • Cardiac hospitalization
  • Maternal death at 6 months
  • Urgent unplanned cardiac hospitalization
  • Elective cardiac interventions (Lysis, ablation, balloon, surgery)
  • Duration of stay in ICU

Obstetric Outcome

  • Mode of delivery (If LSCS – emergency LSCS / elective LSCS, Cardiac indication / obstetric indication)
  • Hypertensive disorders of pregnancy
  • Gestational diabetes
  • Premature rupture of membranes (PROM)
  • Postpartum hemorrhage (PPH)

Fetal/Neonatal Outcome

  • Miscarriage (fetal loss up to 20 weeks)
  • Fetal loss after 20th week
  • Small for gestational age
  • Low birth weight (less than 2.5 kg irrespective of gestational age)
  • Preterm birth
  • Admission to neonatal intensive care unit (NICU)
  • Neonatal death
  • Congenital anomalies (including coronary heart disease) in the newborn

Sample Size

  • Estimated sample size: 2470 (1235 per arm)
  • Assumptions:
    • Composite primary outcome rate: 18% (usual care arm), 13% (intervention arm)
    • Power: 0.8, alpha error: 0.05
    • Intra-class correlation coefficient: 0.01, coefficient of variation in cluster size: 0.7
    • Average cluster size: 56 patients (45-66 patients per site)

Implementation Strategy

  • Site Investigators training: Online mandatory training
  • Enrolment: Patients will be enrolled at participating sites during antenatal care
  • Follow-up: Until 6 weeks after termination of pregnancy, with additional telephonic follow-up for up to 6 months

Data Safety Monitoring Board (DSMB)

  • Regularly assesses and analyzes accumulated study data to ensure participant safety and monitor study conduct

Quality Assurance

  • Central coordinating center ensures data entry and protocol adherence
  • Quality control team reviews de-identified data and provides input to the central coordinating center

Statistical Analysis

  • Logistic regression with robust variance estimates for primary outcomes
  • Multilevel mixed-effects survival models for secondary maternal outcomes
  • Stata and R software used for analysis

Ethical Issues

  • Adheres to ethical principles from the Declaration of Helsinki and ICMR guidelines
  • Participating hospitals will seek local ethics committee approval
  • Written informed consent obtained from all participants

Objective 2

Assess the utility of general and lesion-specific risk assessment tools in predicting outcomes among heart disease in pregnancy.

Study Design

Registry with prospective follow-up

Study Site

50 medical institutions in India caring for pregnant women with heart disease

Methods

  • Pregnant women with confirmed heart disease will be included
  • Data collection:
    • Detailed history
    • Clinical and echocardiographic evaluation
    • Follow-up until 6 weeks post-termination
  • Risk assessment tools:
    • General: mWHO, CARPREG II, M-PAC
    • Lesion-specific: ZAHARA, DEVI

Sample Size

900-1000 patients (expected event rate: 18%, 180 composite events)

Implementation Strategy

  • Online training for site investigators and research staff
  • Operational training manual
  • Patient enrollment during antenatal care
  • Follow-up by combined obstetrics and cardiology teams

Statistical Analysis

Comparison of predictive ability using ROC curve, calibration plot, and decision curve analysis

Ethical Issues

  • Adherence to Declaration of Helsinki and ICMR guidelines
  • Local ethics committee approval
  • Written informed consent from participants

Objective 3

Develop and validate a national risk stratification tool for targeted management of pregnant women with heart disease in India.

Study Design

Registry with prospective follow-up

Study Site

50 medical institutions in India caring for pregnant women with heart disease

Methods

  • Pregnant women with confirmed heart disease will be included
  • Data collection:
    • Detailed history
    • Clinical and echocardiographic evaluation
    • Follow-up until 6 weeks post-termination
  • Risk assessment tools:
    • General: mWHO, CARPREG II, M-PAC
    • Lesion-specific: ZAHARA, DEVI

Sample Size

1615 patients (expected event rate: 12%, 194 events)

Implementation Strategy

  • Online training for site investigators and research staff
  • Operational training manual
  • Patient enrollment during antenatal care
  • Follow-up by combined obstetrics and cardiology teams

Statistical Analysis

  • Univariable and multivariable logistic regression
  • Risk score development using conventional statistical methods and AI-based methods
  • Validation and calibration of risk scores

Ethical Issues

  • Adherence to Declaration of Helsinki and ICMR guidelines
  • Local ethics committee approval
  • Written informed consent from participants