Current Trends and Future Perspectives of Bradycardia, Renal Failure, Atrioventricular Nodal Blockade, Shock, and Hyperkalemia (BRASH) Syndrome: A Narrative Review

Figures

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  Figure 1. Schematic illustration of BRASH syndrome. BRASH: bradycardia, renal failure, atrioventricular (AV) nodal blockade (calcium channel blockers (CCBs) and β-blockers), shock, and hyperkalemia. The pathophysiology of BRASH syndrome is characterized by these components forming a self-perpetuating negative spiral. This schematic was adapted from reference [4] and modified for clarity (with permission) (created using Microsoft PowerPoint (Microsoft Corp., Redmond, WA, USA) and converted to JPEG).

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  Figure 2. Age distribution at the onset of BRASH syndrome. The age of onset ranged from 24 to 97 years. The median and mean ages were 70 and 69.0 ± 15.1 years, respectively, with a negatively skewed distribution (skewness = -0.40). This figure was reconstructed from Table 1, excluding cases with missing data. BRASH: bradycardia, renal failure, atrioventricular nodal blockade, shock, and hyperkalemia.

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  Figure 3. Serial electrocardiograms of a 97-year-old hypertensive female patient with BRASH syndrome. Panels (A), (B), and (C) show ECGs recorded before, immediately after, and one month after the onset of BRASH syndrome, respectively. Panel (B) demonstrates a complete AV block. Following permanent pacemaker implantation, the patient’s intrinsic P waves and QRS complexes are sensed by the device in panel (C), indicating that the complete AV block was reversible. These ECGs are from the first author’s patient [45], with informed consent obtained (unpublished data). BRASH: bradycardia, renal failure, atrioventricular nodal blockade, shock, and hyperkalemia.

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  Figure 4. Serial electrocardiograms of an 89-year-old male patient with dilated cardiomyopathy presenting with BRASH syndrome. Panels (A), (B), and (C) show ECGs recorded before, immediately after, and one month after the onset of BRASH syndrome, respectively. The underlying rhythm is atrial fibrillation throughout, and the ventricular rate was reversibly reduced at the onset of BRASH syndrome. These ECGs are from the first author’s patient [45], with informed consent obtained from the patient’s relatives (unpublished data). BRASH: bradycardia, renal failure, atrioventricular nodal blockade, shock, and hyperkalemia.

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  Figure 5. Distribution of serum creatinine at the onset of BRASH syndrome. Serum creatinine at onset ranged from 1.3 to 13.5 mg/dL (mean ± SD: 3.3 ± 2.4, n = 44), with a markedly positively skewed distribution (skewness = 2.61). Patients undergoing hemodialysis were excluded. This figure was reconstructed from Table 1, excluding cases with missing data. BRASH: bradycardia, renal failure, atrioventricular nodal blockade, shock, and hyperkalemia.

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  Figure 6. Distribution of mean blood pressure at the onset of BRASH syndrome. Mean blood pressure at onset ranged from 40 to 131 mmHg (mean ± SD: 66 ± 18 mmHg, n = 40), with a positively skewed distribution (skewness = 1.24), indicating that most, but not all, patients were hypotensive. Systolic blood pressure is not included. This figure was reconstructed from Table 1, excluding cases with missing data. BRASH: bradycardia, renal failure, atrioventricular nodal blockade, shock, and hyperkalemia.

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  Figure 7. Distribution of serum potassium concentration at the onset of BRASH syndrome. Serum potassium (K+) concentration ([K+]) at onset ranged from 5.4 to 10.1 mmol/L (n = 52). The median [K+] was 6.6 mmol/L, the mode 6.8 mmol/L, and the mean 6.8 ± 1.0 mmol/L, with a positively skewed distribution (skewness = 1.03). Patients undergoing hemodialysis were excluded. This figure was reconstructed from Table 1, excluding cases with missing data. BRASH: bradycardia, renal failure, atrioventricular nodal blockade, shock, and hyperkalemia.

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  Figure 8. Schematic illustration of the pathophysiology of BRASH syndrome in the heart failure pandemic era. This original, hypothetical illustration depicts how contemporary heart failure (HF) therapies may contribute to BRASH syndrome. Angiotensin-converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARB), and mineralocorticoid receptor antagonists (MRA) can exacerbate hyperkalemia, while non-selective β-blockers and non-dihydropyridine calcium channel blockers (CCB) promote bradycardia. Tolvaptan (a vasopressin type 2 receptor antagonist, V2RA) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) may induce hypovolemia, leading to renal failure and delayed drug clearance. Therefore, certain HF medications may contribute to each component of BRASH syndrome. This figure was created using Microsoft PowerPoint (Microsoft Corp., Redmond, WA, USA) and converted to JPEG format. BRASH: bradycardia, renal failure, atrioventricular nodal blockade, shock, and hyperkalemia.

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  Figure 9. Schematic illustration of the pathophysiology of BRASH syndrome in the post-COVID-19 pandemic era. This original, hypothetical illustration depicts how infection with coronavirus disease 2019 (COVID-19) may contribute to BRASH syndrome. In COVID-19, fever and viremic capillary leakage can cause hypovolemia, hemodynamic deterioration, and shock. The infection affects multiple vital organs, including the kidneys, and inflammatory cytokines (interleukins, tumor necrosis factor-α, interferon-γ) contribute to acute kidney injury. Marked cytotoxic effects on somatic cells and renal impairment may result in hyperkalemia. Among these cytokines, IL-6 has been reported to suppress AV conduction [61], and the antiviral drug remdesivir may also induce bradycardia [62,63]. Therefore, both COVID-19 itself and its treatment may contribute to the negative spiral characteristic of BRASH syndrome. This figure was created using Microsoft PowerPoint (Microsoft Corp., Redmond, WA, USA) and converted to JPEG format. BRASH: bradycardia, renal failure, atrioventricular nodal blockade, shock, and hyperkalemia.

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  Figure 10. Distribution of publication years of case reports on BRASH syndrome. This figure shows the number of published case reports of BRASH syndrome by year, illustrating the publication trend over time. BRASH: bradycardia, renal failure, atrioventricular nodal blockade, shock, and hyperkalemia.