Sepsis is a deadly syndrome initiated due to a severe infection, causing abnormal immune reactions that result in inflammation, multiple organ failure, and cardiovascular collapse. This afflicts about 750,000 people each year in America alone and remains the top cause of ICU death around the world [8, 13]. Mayr et al. identified significant racial and health disparities in sepsis epidemiology, noting that Black populations and individuals with preexisting comorbidities experience higher incidence rates and face worse clinical outcomes compared to other groups [12]. Urinary tract infections (UTIs), a common cause of sepsis, can progress to urosepsis when bacteria such as Escherichia coli enter the bloodstream, triggering widespread inflammation [15]. Sepsis is associated with high mortality, particularly in older adults over 70 in developed nations [16]. In rare instances, sepsis leads to cardiovascular collapse with resultant sepsis-induced cardiac arrest (SICA), a less characterized and understudied syndrome that carries a mortality of greater than 70% [10]. With its predominance in non-shockable rhythms and poor resuscitation outcomes, further studies are required to strengthen early identification and treatment.

This case illustrates the life-threatening trajectory of obstructive uropathy secondary to a complicated urinary tract infection (UTI) in a high-risk patient. A 63-year-old nursing home resident with multiple comorbid conditions, including stage 3 chronic kidney disease (CKD), diabetes mellitus, recurrent UTI, and chronic anemia, a developed urosepsis caused by an ESBL-producing E. coli infection. Despite prompt broad-spectrum antibiotics, aggressive fluid resuscitation, and emergent bilateral ureteral stenting to relieve obstruction, she rapidly progressed to septic shock, new-onset atrial fibrillation (AFib) with the rapid ventricular response and subsequent pulseless electrical activity (PEA) arrest. Successful resuscitation required Advanced Cardiovascular Life Support (ACLS) and coordinated intervention by critical care, cardiology, nephrology, infectious disease, and urology teams. This clinical course underscores three crucial lessons: First, patients with CKD, diabetes, and anemia are at heightened risk for sepsis-induced cardiovascular collapse due to baseline metabolic and hemodynamic vulnerabilities. For instance, chronic renal disease in this patient predisposes her to cardiac dysfunction, as seen in cardiorenal syndrome [17]. Second, even timely antimicrobial therapy and source control may fail to prevent cardiac complications in the setting of profound inflammatory and oxidative stress, necessitating proactive cardiovascular monitoring (e.g., continuous telemetry, troponin trends) in septic patients with predisposing conditions [Rudinger]. Finally, multidisciplinary collaboration is essential to address the intersecting infectious, multiorgan pathologies that drive mortality in such cases [18].

The present case highlights the interplay between sepsis-induced cardiac dysfunction (SICA) and its pathophysiological underpinnings—including mitochondrial dysfunction and metabolic dysregulation—emphasizing the urgency of early recognition, protocolized multidisciplinary care, and translational research to address gaps in risk stratification and therapeutic innovation. SICA represents an advanced stage of sepsis-induced myocardial dysfunction characterized by profound hemodynamic instability, systemic inflammation, and acute myocardial depression [10, 11]. Unlike primary cardiac arrests, which are often caused by ischemic heart disease and present with shockable rhythms, SICA predominantly manifests as non-shockable rhythms such as PEA or asystole, making defibrillation ineffective and necessitating immediate ACLS intervention [19]. Complicated UTIs, particularly those associated with obstructive uropathy, prolonged urinary stasis, and recurrent bacterial colonization, sustain systemic inflammation, increasing the risk of cardiovascular collapse [3, 20].

The pathophysiology of SICA is driven by a cascade of inflammatory, metabolic, and microvascular dysfunctions that impair cardiac function. In gram-negative sepsis, endotoxins such as lipopolysaccharides (E. coli LPS) activate Toll-like receptor 4 (TLR4), triggering the release of pro-inflammatory cytokines, including interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) [10,15].). These cytokines induce endothelial damage, vascular leakage, and systemic vasodilation, leading to hypotension and impaired myocardial perfusion [21]. Additionally, cytokine-mediated disruption of calcium homeostasis and mitochondrial dysfunction further reduces cardiac contractility, worsening cardiac output and exacerbating global hypoperfusion [22]. In this patient, the inflammatory cascade likely contributed to acute myocardial depression, evidenced by transient left ventricular dysfunction. The latest findings of Yu et al. 2025 recognize mitochondrial dysfunction and deranged energy metabolism as central mechanisms of sepsis-induced cardiac dysfunction, providing critical insight into potential targets of therapy against the prevention of this lethal complication in critically ill patients [23].

The concurrent presence of AFib further compromised hemodynamic stability, as atrial fibrillation in sepsis is associated with increased mortality due to impaired ventricular filling and loss of atrial contribution to cardiac output [24, 25]. This patient's arrhythmia, most likely the result of autonomic and inflammatory dysregulation electrolyte imbalance, highlights the importance of close cardiac monitoring and early control of rhythm in septic patients. The patient's anemia and CKD are the substrates for her risk of septic cardiac dysfunction. CKD comprises chronic inflammation, electrolyte imbalance, and fluid overload, all of which induce myocardial stress and increased susceptibility to arrhythmias [26]. In addition, anemia compromises oxygen delivery, increasing myocardial hypoxia and ischemic injury. In septic patients, the combined effect of anemia and inflammatory dysregulation increases myocardial stress, worsens cardiac function, and increases the risk of cardiovascular collapse. Effective anemia management through blood transfusion, erythropoiesis-stimulating agents, and close fluid balance monitoring is essential to improving outcomes in critically ill septic patients with CKD [6].

As described by existing literature, Urosepsis demands urgent multidisciplinary intervention, including early antibiotic administration and source control, to address its high mortality rates and prevent progression to life-threatening complications such as sepsis-induced cardiac arrest [Porat, Yang]. Notably, these complications may accelerate disease progression in elderly patients with severe urosepsis, as exemplified in this case [27]. This case underscores the critical role of early recognition, aggressive resuscitation, and multidisciplinary management in sepsis-induced cardiac dysfunction (SICA), aligning with evidence that protocolized, time-sensitive interventions—including ACLS principles, rapid source control (e.g., ureteral stenting), hemodynamic stabilization, and atrial fibrillation (AFib) rate control—reduce mortality in septic shock [9,10]. The success of this approach mirrors findings by existing studies emphasizing coordinated care between critical care and interprofessional teams to mitigate the consequence of sepsis-induced cardiac dysfunction, including end-organ hypoperfusion and secondary cardiac injury, mainly when guided by AFib strategies tailored to sepsis-induced hyperinflammatory states [25, 28].

Future research must prioritize SICA-specific biomarkers, such as mitochondrial dysfunction markers, to enable earlier diagnosis, as proposed, and refine treatment protocols through adaptive trials to address clinical heterogeneity [22]. Machine learning-driven predictive models, akin to frameworks for sepsis-associated AKI, could stratify high-risk patients. At the same time, standardized proactive cardiovascular evaluations (e.g., advanced hemodynamic monitoring) may enhance early intervention [29]. Raising clinical awareness of sepsis-induced cardiac arrest (SICA) and implementing tailored interventions for concurrent infectious, cardiac, and renal pathologies—especially in high-risk populations with comorbidities like CKD and diabetes—are critical to reducing mortality. Translating research on mitochondrial dysfunction into practice remains significant since the case highlights the need for such translation to prevent life-threatening cardiovascular morbidity [22]. It also emphasizes the need for individualized interventions against cardiorenal dysfunction to achieve optimal hemodynamic stability and enhance survival.