Rapid Onset Development of Myocardial Calcifications in the Setting of Renal Failure and Sepsis

Abstract

Myocardial calcifications can arise following damage to myocardial tissue or in the setting of disturbances in the calcium and phosphorus balance. They are associated with a number of cardiac sequelae, as well as higher mortality. Three cases of rapid-onset myocardial calcifications that developed within the course of 5 to 13 weeks in patients who had a history of sepsis and renal failure while undergoing hemodialysis are described. Baseline imaging from several weeks prior without myocardial calcification are shown for each of the three patients, demonstrating the rapid onset of these calcifications. The clinical significance of these findings is discussed.

© RSNA, 2021

Key Points

• ■ Three cases of rapid-onset myocardial calcifications in the setting of sepsis and renal failure, and COVID-19 infection in one patient, are presented.

• ■ These cases highlight the potential for the simultaneous development of dystrophic and metastatic myocardial calcifications due to multifactorial causes.

Introduction

Myocardial calcifications were reported as early as 1908, first at histologic examination, then on chest radiographs, and more recently at chest CT (1–3). Dystrophic calcifications occur in the setting of normal calcium metabolism following myocardial infarction, typically months to years later, due to calcium accumulation within the damaged tissue during the healing process (4). Metastatic calcifications, which occur in previously healthy myocardial tissue, can be present diffusely throughout the myocardium for a variety of reasons and generally involve a disturbance in the physiologic calcium and phosphorus homeostasis. Common causes of metastatic myocardial calcification include acute and chronic renal failure, as well as bone disease (5).

Myocardial calcifications have been found to cause cardiac sequelae such as chamber dilatation, valvular dysfunction, and arrhythmias (6). Myocardial calcifications are therefore often associated with poor prognosis and high mortality. Here we present three patients who developed rapid and fairly diffuse myocardial calcification at chest CT in the setting of chronic kidney disease and sepsis. Each patient had undergone CT imaging several weeks previously that demonstrated no myocardial calcifications. Previous case reports have described myocardial calcifications arising within a span of weeks in the setting of sepsis or chemotherapy (7–14). In contrast, myocardial calcifications that develop secondary to calcium and phosphorus disturbances have been reported to occur more gradually, over the span of months to years (15,16). Given the association of myocardial calcifications with adverse outcomes, it is important to recognize the phenomenon of rapid myocardial calcification and understand the clinical characteristics and mechanisms that lead to their development.

Case Presentations

Case 1

A 34-year-old White woman with a history of end-stage renal disease was transferred from an outside hospital in septic shock. At the outside hospital, the patient had undergone exploratory laparotomy and had a postoperative course complicated by cardiac arrest and acute respiratory distress syndrome. Upon transfer, she was receiving maximum pressor support and broad-spectrum antibiotics, and continuous venovenous hemofiltration was started on day 2 of admission.

On day 3 of admission, chest CT was performed to evaluate the progression of the acute respiratory distress syndrome, and diffuse calcification in the left ventricular lateral wall and septum, as well as the right ventricle, were found. The average attenuation value of the calcifications was 542 HU. There were also calcifications found in the soft tissues of the presternal and left infrascapular regions and in the left lobe of the liver. These findings were new when compared with a chest CT performed 5 weeks previously for an unknown indication. Baseline and follow-up CT scans are shown in Figure 1.

Figure 1:

Images in a 34-year-old woman with end-stage renal disease and septic shock. A, Prior axial non–contrast-enhanced chest CT scan with no evidence of myocardial calcifications. B, Axial non–contrast-enhanced chest CT scan at similar level acquired 36 days later shows marked calcification in the left ventricular lateral wall, interventricular septum, and right ventricle (arrows).

During the index admission, the patient’s calcium levels were consistently low, between 7.3 and 7.9 mg/dL (reference: 8.6–10.2 mg/dL); her phosphorus levels were consistently high, from 5.4–8.0 mg/dL (reference: 2.5–4.5 mg/dL); and her creatinine levels were consistently high, from 1.81–3.58 mg/dL (reference: 0.66–1.25 mg/dL).

Despite aggressive treatment of her septic shock and pulmonary and renal failure, the patient’s clinical status continued to decline. She went into cardiac arrest and died on day 6 of admission.

Case 2

A 20-year-old man (race unspecified) with a history of trisomy 21, atrial and ventricular septal defects, and a patent ductus arteriosus was transferred from an outside hospital, where he was diagnosed with COVID-19, for initiation of venovenous extracorporeal membrane oxygenation. He developed persistent hypotension, requiring pressors, and acute renal failure 1 week into admission, necessitating continuous renal replacement therapy.

A chest CT performed 2 months into his admission for worsening hypercarbia in the setting of acute respiratory distress syndrome and COVID-19 pneumonia showed increased attenuation of the left heart myocardium consistent with calcium deposition. The average attenuation value of the calcification was 97 HU. Myocardial calcification was absent on a CT scan 5 weeks earlier obtained for worsening acute respiratory distress syndrome secondary to COVID-19 pneumonia. Scans are shown in Figure 2.

Figure 2:

Images in a 20-year-old man with history of trisomy 21 and recent diagnosis of COVID-19 pneumonia with development of dystrophic myocardial calcifications in the left heart within 5 weeks. A, Axial non–contrast-enhanced chest CT scan with no evidence of myocardial calcifications. B, Axial non–contrast-enhanced chest CT scan obtained 40 days later shows dystrophic deposition of calcium in the left ventricular lateral wall myocardium (arrow).

During admission, the patient’s calcium levels remained within normal limits at 9–10 mg/dL until 3 days before the CT scan was obtained, when they began to increase, ranging from 10.5 to 11.5 mg/dL (reference: 8.6–10.2 mg/dL). His phosphorus levels were consistently high at 5.3–6.5 mg/dL (reference: 2.5–4.5 mg/dL). His creatinine level was low at 0.4–0.5 mg/dL (reference: 0.66–1.25 mg/dL).

The patient recovered from COVID-19 and was weaned off venovenous extracorporeal membrane oxygenation and mechanical ventilation. To date, the patient’s respiratory status has continued to gradually improve with the use of a tracheostomy collar, and he has not developed any signs of cardiac dysfunction.

Case 3

A 30-year-old White man with a history of end-stage renal disease requiring hemodialysis 15 months previously, subsequently with noncompliance, and multidrug-resistant bacteremia presented to our hospital with open wounds in bilateral lower extremities and missed hemodialysis. The patient was hypotensive in the emergency department and required an epinephrine drip. He also received hemodialysis starting on day 1 of admission.

A chest CT was performed for possible pneumonia suspected at chest radiography on the day of admission. The CT scan showed calcium deposition within the papillary muscles and the lateral wall of the left ventricle. The average attenuation value of the calcification was 176 HU. Dual-energy CT allowed for calcium suppression, which confirmed the presence of calcium in the myocardium. There were also calcified thrombi within the left and right pulmonary arteries and within the collapsed bilateral lower lobes of the lung and airway-centered calcification in the right upper lobe and lingula. A CT scan obtained 13 weeks earlier showed calcified thrombus in the right pulmonary artery but no other regions of calcification. In particular, there were no calcifications within the myocardium on the earlier scan. Baseline and follow-up CT scans, as well as a calcium-suppressed scan, are shown in Figure 3.

Figure 3:

Images in a 30-year-old man with end-stage renal disease who developed dystrophic myocardial calcifications in the left heart within 13 weeks. A, Prior axial non–contrast-enhanced chest CT scan with absence of myocardial calcifications. B, Axial non–contrast-enhanced chest CT scan acquired 93 days later shows interval development of calcium deposition within the lateral wall of the left ventricle and papillary muscle (arrows). C, Dual-energy CT scan with calcium-suppression demonstrates low attenuation confirming the presence of calcium deposition in the left ventricle and papillary muscle (arrows).

During admission, the patient’s calcium levels ranged from low to normal at 7.6 to 8.9 mg/dL (reference: 8.6–10.2 mg/dL). His phosphorus levels were consistently high at 7.5 to 8.2 mg/dL (reference: 2.5–4.5 mg/dL). His creatinine level was consistently high at 4.18–6.27 mg/dL (reference: 0.66–1.25 mg/dL).

The patient was admitted to the medical intensive care unit for management of his end-stage renal disease requiring dialysis. He signed out against medical advice after receiving two hemodialysis treatments.

Discussion

We report here three patients with rapid onset of myocardial calcification. One striking and highly unusual feature of each of our three patients is that baseline and follow-up CT imaging were available to show the rather rapid interval development of myocardial calcification. The attenuation value of the calcification in each of the three cases exceeded that of the upper limit for normal myocardium (17).

Several reports have described metastatic calcifications arising in patients with chronic renal failure due to hyperphosphatemia and secondary hyperparathyroidism, which subsequently leads to hypercalcemia (4,6,15,18). A possible explanation is that patients in acute renal failure are initially hypocalcemic due to an inability to produce 1,25-(OH)₂D₃ (the active form of vitamin D), leading to hyperparathyroidism, but upon entering the recovery phase are able to better respond to increased parathyroid hormone levels and therefore develop hypercalcemia and subsequently myocardial calcifications (19,20). Hemodialysis has also been shown to cause calcium and phosphorus imbalances, which may contribute to the development of myocardial calcifications. However, the imbalances caused by end-stage renal disease and hemodialysis therapy are typically thought to cause more insidious development of calcifications, rather than onset within weeks as seen in our patients (15,16). Additionally, the clinical courses of our patients were not indicative of renal disease and hemodialysis as the sole causes of myocardial calcification. Although two of the three patients had end-stage renal disease at the time of the CT scan showing myocardial calcification, the diagnosis was also present at the time of the baseline scans, where no myocardial calcifications were seen.

Sepsis has also been associated with myocardial calcification. Isolated case reports have described the onset of myocardial calcifications in patients with sepsis who had undergone CT imaging 4 to 10 weeks previously without calcifications (7–11,13,14). Of our patients, one was in septic shock, and the other two patients had prolonged, multiweek histories of sepsis. Moreover, each of our patients was receiving pressor therapy, with two patients requiring pressors for sepsis-related hypotension. Pressor therapy may be the cause of dystrophic calcifications occurring within weeks, as previous reports have posited that the high catecholamine level can directly lead to myocardial ischemia and necrosis, which then lays the groundwork for calcium deposition (21,22).

It is worth noting that one of our patients originally presented with COVID-19 pneumonia. Recent studies have documented several cardiovascular complications in patients with COVID-19, including myocarditis, pericarditis, and cardiac arrest (23,24). However, to our knowledge, this is the first reported case of myocardial calcifications developing in a patient with COVID-19. It is possible that the proinflammatory state induced by viral infection contributed to the development of calcifications by a similar pathway as sepsis-induced myocardial damage.

Given the relatively short time of onset of calcifications in all three patients, it is likely that a relatively acute process, such as sepsis causing myocardial damage, led to the deposition of dystrophic calcifications. If the disturbances in calcium and phosphorus metabolism secondary to renal failure or chronic hemodialysis were solely responsible for the calcifications, a more gradual onset would have been expected. Reports of histologic examination of both dystrophic and metastatic calcifications have described identical findings of hydroxyapatite formation that begins in the mitochondria and subsequently extends throughout the rest of the myocardial fibers (25). It has therefore been proposed that dystrophic and metastatic calcifications develop through a shared mechanism in which calcium enters myocardial fibers, whether through an increased concentration gradient secondary to hypercalcemia or through a cell membrane defect secondary to prior muscle damage, and initially becomes sequestered by the mitochondria but eventually accumulates throughout the muscle fibers when homeostatic efforts are overwhelmed (25). This shared mechanism of calcification suggests that it is possible that an acute insult such as inflammation secondary to sepsis was superimposed on a baseline abnormality in calcium and phosphorus, which increased the susceptibility of developing myocardial calcifications in our patients. To our knowledge, there has been only one other reported case of a similar patient with a history of chronic kidney disease who developed rapid onset myocardial calcifications following septic shock (26). Given that sepsis is a relatively common diagnosis and myocardial calcifications are a considerably rarer finding, it seems likely that multiple factors contribute to the ultimate development of myocardial calcifications in patients with sepsis (27).

In conclusion, the calcifications that developed in our three patients are consistent with the definition of dystrophic calcifications, because a probable source of damage to the myocardium can be identified. However, given that all three patients had a history of chronic kidney disease with calcium and phosphorus disturbances, there is likely also a component of metastatic myocardial calcification in these patients. These cases demonstrate the complex pathophysiologic processes underlying the development of myocardial calcification and facilitate a clearer understanding of the clinical setting and time course over which they can develop.