The diagnosis of atrial fibrillation–mediated cardiomyopathy is currently difficult, and when atrial fibrillation–mediated cardiomyopathy progresses to the point where the myocardial lesions are irreversible, cardiac function does not improve significantly despite ventricular rate or rhythm control. In addition, in patients with a combination of other types of cardiomyopathy, atrial fibrillation may further worsen cardiac function, and the improvement in cardiac function may be masked in these patients when the ventricular rate is controlled. In some patients, paroxysmal atrial fibrillation is the main manifestation, and because of the short duration of the episodes, they did not seek medical attention in time until they develop cardiac insufficiency. The above reasons make the diagnosis of atrial fibrillation–mediated cardiomyopathy more difficult. Therefore, this study combined with the actual clinical situation, it must be clear that atrial fibrillation is the only cause of unexplained heart failure or causes deterioration of heart failure before the patients are enrolled. It was also combined with the patient's clinical history such as the temporal relationship between new onset of atrial fibrillation or increased atrial fibrillation load and the occurrence of cardiomyopathy: new onset of heart failure after atrial fibrillation that could not be explained by other causes; the simultaneous occurrence of heart failure and atrial fibrillation; the recovery of cardiac function after rhythm or ventricular rate control; the rapid deterioration of cardiac function after the recurrence of atrial fibrillation; and the rapid decrease of BNP level after the restoration of sinus rhythm or ventricular rate control in atrial fibrillation.
There is still controversy about the target heart rate target values in patients with atrial fibrillation–mediated cardiomyopathy. In the RACE II study published in NEJM in 2010 [3], 614 patients with permanent atrial fibrillation were randomly assigned to either a lenient strategy (resting heart rate < 110 bpm) or a strict strategy (resting heart rate < 80 bpm and mild exercise < 110 bpm) with the primary endpoint set at cardiac death, heart failure hospitalization, stroke, systemic embolism, and bleeding with a composite endpoint of fatal arrhythmia. After 3 years of follow-up, 86% of the target heart rate was achieved in the lenient strategy group and only 53% of the target heart rate was achieved in the strict strategy group. The primary endpoint eventually occurred in 12.9% of the lax strategy group and 14.9% of the strict strategy group, with the lax strategy not inferior to the strict strategy (the non-inferiority threshold was set at -2%). In subsequent analyses, cardiac remodeling and quality of life were also not significantly different between the two strategies. Therefore, a more lenient ventricular rate control strategy was adopted in this study, with a target ventricular rate control goal of < 110 bpm at rest, but more stringent ventricular rate control may be considered if patients have significant symptoms, deteriorating left ventricular function, or a CRT in place despite the lenient goal.
Although the current CASTLE-AF study, a prospective randomized controlled trial in the field, confirmed[4] that 363 patients with heart failure combined with atrial fibrillation were randomized into catheter ablation and drug treatment groups, the primary composite endpoint (all-cause mortality + heart failure worsening rehospitalization rate) decreased by 16.1% in the catheter ablation group and catheter ablation treatment was superior to drug treatment. However, recurrent recurrences may still exist with rhythm control, whereas ventricular rate control has the advantage of being safe, effective, and easily accepted by patients. Besides, the 2019 ACC/AHA guidelines for the management of atrial fibrillation include ventricular rate control as the first-line treatment option for patients with atrial fibrillation–mediated cardiomyopathy[5]. Therefore heart rate control should be used as a basic treatment for rhythm control. Although β-blockers are the most widely used ventricular rate control agents for atrial fibrillation, some studies have shown that β-blockers do not reduce mortality in patients with atrial fibrillation combined with heart failure[6].
Diltiazem hydrochloride is a non-dihydropyridine calcium channel blocker and is recommended in guidelines as a first-line agent for ventricular rate control along with beta-blockers. Because of the limited use of diltiazem hydrochloride in patients with heart failure with an ejection fraction of less than 40% and the presence of some negative inotropic effects, there is a gap in clinical studies on the prognosis of patients with atrial fibrillation–mediated cardiomyopathy with the use of diltiazem hydrochloride. In the present study, the target heart rate compliance rate, left ventricular ejection fraction, ProBNP improvement and 30-day readmission rate in the experimental group with diltiazem were significantly better than those in the control group, indicating that diltiazem hydrochloride has a protective effect on patients with atrial fibrillation–mediated cardiomyopathy. Although diltiazem hydrochloride has some negative inotropic effects, there was no significant increase in the short-term deterioration rate of cardiac function in the experimental group in this study, which is generally consistent with its safety profile reported in previous similar studies[7]. The mechanism of the protective effect of diltiazem hydrochloride in patients with atrial fibrillation–mediated cardiomyopathy is not well understood, and it may be related to factors such as controlling the rapid ventricular rate by inhibiting the atrioventricular node, increasing myocardial tissue perfusion, and thus improving diastolic function; improving abnormal calcium regulation and reducing myocardial remodeling through calcium channel blockade.
In this study, a quadruple combination of standardised drug therapy with diltiazem was shown to be superior to the classic three-drug Golden Triangle regimen in patients with atrial fibrillation cardiomyopathy without previous organic heart disease, and significantly improved cardiac function and short-term prognosis in patients with atrial fibrillation cardiomyopathy in the short term. Therefore, the quadruple combination of diltiazem is expected to become a standardised treatment for patients with atrial fibrillation cardiomyopathy in the future. This study also provides a new approach to the clinical management of patients with heart failure combined with atrial fibrillation. Before treating a patient with heart failure combined with atrial fibrillation, we need to first ask the patient about the timing of the onset of atrial fibrillation in relation to the onset of cardiomyopathy in order to initially determine whether the patient has atrial fibrillation cardiomyopathy. If atrial fibrillation cardiomyopathy is present we can offer patients a more individualised quadruple therapy than classical drug therapy.In summary, diltiazem hydrochloride can effectively improve cardiac function and prognosis in patients with atrial fibrillation–mediated cardiomyopathy, and is a safe and effective method.