Clinical trial NCT06039072: Clinical Observation of Long-term Cardiac Function Prognosis in Patients With PPCM Who Have Recovered Cardiac Function
Official title: Clinical Observation on the Prognosis of Long-term Cardiac Function by Drug Withdrawal in Patients With Peripartum Cardiomyopathy With Cardiac Function Recovery
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Cardiomyopathy, Dilated
Lead sponsor: Qilu Hospital of Shandong University
Sponsor class: OTHER
First posted: 2023-09-15
Enrollment: 120
Sex: FEMALE
Minimum age (years): 20
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Source Clinical case collection of peripartum cardiomyopathy in multiple hospitals and recruitment of patients with peripartum cardiomyopathy，with recovery of cardiac function after standardized treatment.

Brief summary: Peripartum cardiomyopathy (PPCM) is an idiopathic cardiomyopathy that occurs in late pregnancy and early postnatal period, which is mainly characterized by varying degrees of impaired ventricular systolic function and symptoms related to heart failure, and is a serious threat to maternal health. About 50% of patients can achieve complete recovery of cardiac function within 6 months after diagnosis with early standardized treatment, about 30%-40% of patients can have delayed recovery, and about 12.6% of patients have long-term impairment of cardiac function and poor prognosis. However, there are still controversies about whether and when to stop the drug after standardized treatment. The Chinese Society of Cardiovascular Disease of the Chinese Medical Association proposed in the Guidelines for the Diagnosis and Treatment of Dilated Cardiomyopathy in China that patients with PPCM should be considered for gradual withdrawal of the drug after at least 1 year of stabilization of cardiac structure and function recovery. And in the China Heart Failure and Diagnostic and Treatment Guidelines released in the same year, it is proposed that standardized heart failure therapy for patients with peripheral cardiomyopathy should be continued until at least 6 months after the left ventricular function has been fully recovered before gradual discontinuation of the drug. The American Heart Association's 2019 guidelines for perinatal cardiomyopathy remain skeptical about the timing of discontinuation, with some experts suggesting that the drug can be gradually discontinued 1-2 years after cardiac function has recovered, while others still recommend long-term use of the drug to avoid deterioration of cardiac function after discontinuation. At present, there is a lack of large-scale clinical studies on the effect of stopping standardized treatment on the long-term prognosis of PPCM patients, and clarifying whether PPCM patients can discontinue the drug and the timing of discontinuation is of great significance to the long-term prognosis of the patients and even to the rational allocation of the national healthcare resources as a whole.

Detailed description: To clarify the effects of continuing standardized therapy and discontinuing standardized drug therapy on long-term cardiac function in patients with perinatal cardiomyopathy 1 year after cardiac function has been restored and stabilized, and to provide more theoretical and clinical bases for the therapeutic regimen of patients with perinatal cardiomyopathy after cardiac function is restored.

After diagnosis, patients received standardized heart failure treatment: according to the perinatal cardiomyopathy diagnosis and treatment guidelines of the Cardiovascular Disease Branch of the Chinese Medical Association and the American Heart Association, standardized heart failure treatment and symptomatic treatment were carried out according to the individualized differences of the patients, and for those who developed the disease in pregnancy, non-contraindicated medication was applied before delivery, and the appropriate mode of delivery was selected according to the gestation week and the cardiac function of the patient and the condition of the fetus, and the patients were given a comprehensive decision on the treatment plan by our hospital and the cardiologists and obstetricians of the collaborating hospitals. Cardiologists and obstetricians from our hospital and collaborating hospitals made comprehensive decisions on the treatment plan for the patients. The cardiologists and obstetricians of our hospital and the collaborating hospitals will make a comprehensive decision on the treatment plan of the patients. We will also assess whether the patients are suitable for breastfeeding, and choose non-contraindicated drugs and drugs with low milk concentration for breastfeeding, and standardize heart failure treatment as soon as possible after breastfeeding is finished; and for the non-breastfeeding patients, we will carry out the anti-heart failure treatment, applying the drugs such as ACEI/ARB, MRA and β-blocker as early as possible, and adjusting the dosage gradually according to the principle of individualization.

Treatment regimen for subjects in the discontinuation group: subjects received a combination of ACEI/ARBs, β-blockers, MRAs and diuretics during the standardized treatment phase, and after recovery of cardiac function, in order to avoid adverse effects on cardiac function caused by sudden withdrawal of medication, the medication was gradually discontinued in accordance with the protocol.

The completed case observation forms from each test center were retrieved after review by the supervisors and handed over to the main responsible unit (i.e., Qilu Hospital of Shandong University) for data processing. Data on the case report forms were entered in double copies by two persons, and the database was locked after verification to confirm that there were no errors. Measurement data were described by mean and standard deviation, and count data were described by number of cases and percentage. SPSS.23.0 statistical software was applied to statistically analyze the intention-to-treat set and the protocol-compliant set, respectively. The demographic characteristics of the enrolled cases in the two sets were first analyzed at baseline to examine the balance and comparability of the two sets. Then the effectiveness indicators and safety indicators of the two groups were compared.

For each index in the UCG, ECG, and a number of indicators such as blood pressure and heart rate between the experimental group and the control group; quantitative information was compared using the t-test for two-sample comparisons in a paired group design. At the same time, subgroup analyses were set up based on the NT-proBNP values of the patients and the time required for recovery of cardiac function, and univariate and multivariate statistical analyses were performed, and the primary endpoints were analyzed using the Kaplan-Meier survival curves with the log-rank-sum test, and the rank-sum tests for the group-designed two-sample comparisons were used for the NYHA classification and KCCQ scores. All statistical tests were two-sided, and a p-value less than or equal to 0.05 was considered statistically significant for the differences tested.

Eligibility criteria: Inclusion Criteria:

Perinatal cardiomyopathy patients aged 20-45 years who meet the diagnostic criteria for perinatal cardiomyopathy, i.e.: heart failure and left ventricular systolic hypoplasia occurring in the last trimester of gestation or 5 months postpartum; no previous history of heart failure and other etiologies that could explain the heart failure; impaired left ventricular function as indicated by cardiac ultrasound: LVEF \<45% and/or FS \<30% or left ventricular end-diastolic internal diameter ( LVEDd) \> 5.0 cm; (ii) Those who have been diagnosed with perinatal cardiomyopathy and are now receiving standardized drug therapy, and whose cardiac function has not yet recovered, and whose enrollment time is not more than 1 year from the time of diagnosis.

Exclusion Criteria:

(i) Those with a previous history of severe organic valvular disease; (ii) Those with a previous history of diabetes mellitus, chronic hypertension and thyroid disease;

* Those with history of congenital heart disease, ischemic cardiomyopathy and other cardiomyopathies; ④ Those with severe infections and impaired liver and kidney functions (eGFR \<30ml/min/1.73m2, or transaminases more than 5 times higher than the upper limit of normal values); ⑤ Those with previous persistent atrial, supraventricular or ventricular arrhythmia and have to be treated with anti-arrhythmic drugs for a long time; (vi) Those with serious adverse reactions and contraindications to heart failure therapeutic drugs.

Primary outcomes:
measure: deterioration in cardiac function within 1 year of the subgroup study
timeFrame: 1 year
Secondary outcomes:
measure: patient cardiovascular accidents, rehospitalization-related adverse events
timeFrame: 1 year
Other outcomes:
Locations:
Study officials:
affiliation: Qilu Hospital of Shandong University
name: Xiaoping ji
role: STUDY_CHAIR
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