Cardiac Complications of Human Babesiosis

Abstract

Background

Human babesiosis is a worldwide emerging tick-borne disease caused by intraerythrocytic protozoa. Most patients experience mild to moderate illness, but life-threatening complications can occur. Although cardiac complications are common, the full spectrum of cardiac disease and the frequency, risk factors, and outcomes in patients experiencing cardiac complications are unclear. Accordingly, we carried out a record review of cardiac complications among patients with babesiosis admitted to Yale–New Haven Hospital over the last decade to better characterize cardiac complications of babesiosis.

Methods

We reviewed the medical records of all adult patients with babesiosis admitted to Yale–New Haven Hospital from January 2011 to October 2021, confirmed by identification of Babesia parasites on thin blood smear and/or by polymerase chain reaction. The presence of Lyme disease and other tick-borne disease coinfections were recorded.

Results

Of 163 enrolled patients, 32 (19.6%) had ≥1 cardiac complication during hospitalization. The most common cardiac complications were atrial fibrillation (9.4%), heart failure (8.6%), corrected QT interval prolongation (8.0%), and cardiac ischemia (6.8%). Neither cardiovascular disease risk factors nor preexisting cardiac conditions were significantly associated with the development of cardiac complications. The cardiac complication group had a greater prevalence of high-grade parasitemia (>10%) (P < .001), longer median length of both hospital (P < .001) and intensive care unit stay (P < .001), and a higher mortality rate (P = .02) than the group without cardiac complications.

Conclusions

Cardiac complications of acute babesiosis are common and occurred in approximately one-fifth of this inpatient sample. Further investigation is needed to elucidate the relationship between babesiosis severity and cardiac outcomes.

Of 163 hospitalized patients with babesiosis, 20% had ≥1 cardiac complication, including atrial fibrillation and heart failure. Complications were associated with longer hospital and intensive care unit stay and a higher mortality rate. Cardiac complications of severe babesiosis are common and increase disease health burden.

Human babesiosis is a worldwide emerging tick-borne disease caused by intraerythrocytic protozoal parasites in the genus Babesia [1–5]. The most common cause is Babesia microti, which is endemic in the United States and China and found sporadically in Europe and much of the rest of the world [1–3]. Most patients experience a mild to moderate illness that resolves after a week of azithromycin and atovaquone [1–8]. Severe disease that requires hospital admission and predisposes patients to life-threatening complications occurs most often in immunocompromised patients who are >50 years of age [1, 7, 9, 10]. More than a third of hospitalized patients experiencing B. microti infection develop complications that include cardiac disease, acute respiratory distress syndrome (ARDS), disseminated intravascular coagulopathy (DIC), severe hemolytic anemia, coma, shock, renal failure, splenic rupture, and death [2, 4, 11–16].

Cardiac complications of babesiosis that include congestive heart failure, arrhythmia, ischemic heart disease and myocarditis, are important causes of morbidity that can lead to death [4, 7, 13, 17]. The full spectrum of cardiac complications associated with babesiosis is unclear, including the etiology, frequency, and risk factors of cardiac pathology [7, 13, 14, 18–20]. Accordingly, we carried out a retrospective record review of cardiac complications among all patients with babesiosis admitted to Yale–New Haven Hospital (YNHH) in New Haven, Connecticut, over the last decade. Our primary objectives were to determine the type and frequency of cardiac complications among patients hospitalized for babesiosis and to identify risk factors for these complications. We hypothesized that the prevalence of cardiac complications is higher among patients with a past medical history of cardiac disease and that use of medications associated with QT interval prolongation or arrhythmia, advanced age, and high parasitemia (>10%) are associated with cardiac complications.

METHODS

Study Design and Patient Selection

We reviewed the medical records of all adult patients (≥18 years) admitted to YNHH from January 2011 to October 2021 with a diagnosis of babesiosis. Eligible patients were identified in collaboration with the Yale Center for Clinical Investigation Joint Data Analytics Team. A babesiosis diagnosis was confirmed by identification of Babesia parasites on thin blood smear and/or amplification of B. microti DNA by polymerase chain reaction (PCR). A diagnosis of Lyme disease was based on the presence of an erythema migrans rash and/or a 4-fold rise in Lyme disease antibody. A diagnosis of Anaplasma phagocytophilum infection (human granulocytic anaplasmosis) was based on a positive PCR blood test result for this condition.

Data Collection

Manual record reviews were performed. Demographic variables and specific cardiovascular risk factors were abstracted. Details of all preexisting cardiac diseases were recorded, including arrythmia, conduction disease, heart failure, coronary artery disease, myocardial infarction, cardiomyopathy, and valvular abnormalities. The management of cardiac conditions, including medication use, percutaneous interventions, and surgical intervention, was thoroughly reviewed and abstracted.

Variables pertaining to hospital admissions for babesiosis treatment were also abstracted, including length of hospital and intensive care unit (ICU) stays, deaths, and causes of death. Variables relating to the medical management of babesiosis included peak parasitemia, red blood cell (RBC) exchange transfusion, and antimicrobial therapy. If a medication was changed during the hospital admission, we evaluated whether the change was directly or indirectly related to a concern about cardiac complications, especially arrythmia and prolongation of the corrected QT interval.

We recorded all new cardiac complications and exacerbations of preexisting cardiac conditions as defined by diagnostic criteria established by guideline standards [21–23]. The presence of complications was derived from physician documentation, vital signs, and laboratory results that included B-type natriuretic peptide or N-terminal pro–B-type natriuretic peptide, troponins), electrocardiograms [ECGs], and transthoracic echocardiograms. All ECGs and echocardiograms were manually reviewed and interpreted by a cardiologist (E. O.).

Specific parameters were abstracted from transthoracic echocardiograms and ECGs, including ejection fraction and interval measurements. QT intervals were measured manually from the earliest QRS deflection to the end of the T wave. The tangent method was used to define the end of the T wave. The QT intervals were then corrected for heart rate using Bazett’s formula [22]. For patients with QRS duration >120 milliseconds, JT and corrected JT (JTc) intervals were obtained (JT = QT − QRS; JTc = QTc − QRS). Corrected QT (QTc) interval prolongation was defined as absolute QTc interval >500 milliseconds (or JTc interval >410 milliseconds) or increase in QTc interval prolongation from baseline by 60 milliseconds. At the time of QTc interval prolongation, several parameters were recorded, including electrolyte levels, antibiotic regimen, concomitant use of medications associated with QT interval prolongation, and occurrence and treatment of any clinical arrhythmias, such as torsade de pointes.

Ethical Approval

This study was approved by the Yale University Human Investigation Committee.

Statistical Analyses

Statistical analyses were performed using SAS Studio 3.8 software. Demographic and clinical characteristics of the sample were summarized using appropriate descriptive statistics. Patients were categorized according to the presence or absence of cardiac complications, and the 2 groups were compared. Differences in patient demographic and clinical characteristics between groups were tested for significance using the Mann-Whitney U test for continuous variables and χ² tests for categorical variables. Fisher exact test was used where there were <5 samples in a given category.

RESULTS

Study Population

A total of 163 patients met the criteria for inclusion in this study. Demographic characteristics of the study sample are shown in Table 1. The patients’ median age was 67.0 years (interquartile range [IQR], 22.0 years; range, 30–93 years). The study population was predominantly male (n = 104 [63.8%]), white (n = 118 [74.7%]), and non-Hispanic/non-Latino (n = 143 [89.4%]). Patients who experienced cardiac complications differed from those without complications with respect to median (IQR) age at diagnosis (72.5 years [18.5] vs 66.0 years [22.0] years; P = .005), race (P = .050, and ethnicity (P = .04) (Table 1).

Table 1.

Demographic Characteristics of the Study Sample

Characteristic	Patients, No. (Column %)a			P Valueb
	All Patients (n = 163a)	Cardiac Complications
		Yes (n 32)	No (n = 131)
Age, median (IQR), y	67.0 (22.0)	72.5 (18.5)	66.0 (22.0)	.005c
Sex
ȃMale	104 (63.8)	21 (65.6)	83 (63.4)	.81
ȃFemale	59 (36.2)	11 (34.4)	48 (36.6)
Raced
ȃWhite	118 (74.7)	27 (90.0)	91 (71.1)	.050
ȃBlack/African American	12 (7.6)	0 (0.0)	12 (9.4)
ȃAsian or Pacific Islander	14 (8.9)	3 (10.0)	11 (8.6)
ȃOther	14 (8.9)	0 (0.0)	14 (10.9)
Ethnicityd
ȃHispanic or Latino	17 (10.6)	0 (0.0)	17 (13.1)	.04c
ȃNon-Hispanic/non-Latino	143 (89.4)	30 (100.0)	113 (86.9)

Abbreviation: IQR, interquartile range.

Data represent no. (column %) unless otherwise specified; column percentages may not add up to 100% owing to rounding.

Analysis of variance was assessed using Mann-Whitney U test for continuous variables and χ² test for categorical variables; Fisher exact test was used when there were <5 samples in a given category.

Significant at P < .05.

Numbers may not add up to column totals owing to missing data (race was unknown in 5 patients, and ethnicity in 3).

Cardiac Complications

The frequencies of cardiac complications during babesiosis hospitalization are displayed in Table 2. In total, 32 (19.6%) patients experienced ≥1 cardiac complication during admission. Cardiac complications included supraventricular arrhythmias (10.4%), heart failure (8.6%), QTc interval prolongation (8.0%), cardiac ischemia (6.8%), ventricular arrhythmias (1.2%), and valvular complications (1.2%) (Table 2). Of the patients who experienced supraventricular arrhythmias, 10 had new-onset atrial fibrillation and 5 had exacerbations of preexisting atrial fibrillation (ie, atrial fibrillation with rapid ventricular response). Four patients had new-onset atrial flutter, and 1 had atrial tachycardia. Ventricular arrhythmias were also documented in 2 patients—1 with monomorphic ventricular tachycardia and 1 with torsades de pointes.

Table 2.

Frequency of Cardiac Complications During Hospitalization for Babesiosis

Cardiac Complication	No. With Complication	Proportion With Complication, %a
		Cardiac Complication Group (n = 32)	All Patients (n = 163)
Supraventricular arrhythmiab	17	53.1	10.4
ȃAtrial fibrillation
ȃȃPreexisting atrial fibrillation; rapid ventricular response	5	15.6	3.1
ȃȃNew onset	10	31.3	6.1
ȃAtrial flutter (new onset)	4	12.5	2.5
ȃAtrial tachycardia	1	3.1	0.6
ȃOtherc	1	3.1	0.6
Ventricular arrhythmia	2	6.3	1.2
ȃMonomorphic ventricular tachycardia	1	3.1	0.6
ȃTorsades de pointes	1	3.1	0.6
QTc interval prolongation (without torsade de pointes)	13	40.6	8.0
Heart failure	14	43.8	8.6
ȃNew onset	11	34.4	6.8
ȃȃNewly reduced ejection fraction	6	18.8	3.7
Cardiac ischemia	11	34.4	6.8
ȃType I NSTEMI	1	3.1	0.6
ȃType II NSTEMI	10	31.3	6.1
Valvular disease	2	6.3	1.2
ȃMitral regurgitation	2	6.3	1.2

Abbreviations: NSTEMI, non–ST elevation myocardial infarction; QTc, corrected QT.

Percentages do not add up to 100% because some patients had multiple cardiac complications.

Multiple supraventricular arrhythmias occurred in 3 patients.

Reentrant tachycardia.

Of the 163 study patients, 134 (82%) had ≥1 ECG performed. QTc interval prolongation was identified on the ECGs of 13 of 89 (14.6%) patients who received an ECG while on antibiotics for ≥24 hours, including the patient who experienced torsades de pointes. New-onset heart failure was found in 11 patients (6.8%), with newly reduced ejection fraction noted in 6 (3.7%). An echocardiogram was obtained in 41 patients (25%), with or without an ECG. Cardiac ischemia was noted in 11 patients, 1 with type 1 non–ST elevation myocardial infarction (NSTEMI) and 10 with type 2 NSTEMI. New significant valvular disease was documented in 2 patients, both of whom had severe mitral regurgitation during admission. One of them experienced a chordal rupture with subsequent flail mitral leaflet and severe mitral regurgitation. In the second patient, ischemic mitral regurgitation developed after type 1 NSTEMI and ischemic cardiomyopathy with reduced ejection fraction.

Possible Risk Factors for Development of Cardiac Complications

We assessed the relationship between known cardiovascular disease risk factors and the development of cardiac complications (Table 3). Preexisting cardiac conditions including coronary artery disease, arrhythmia, heart failure and cardiomyopathy, baseline conduction disease, and valvular disease were not associated with the emergence of cardiac complications. Other comorbid conditions—including chronic kidney disease, chronic obstructive pulmonary disease, and 12 cases of Lyme disease coinfection—also did not differ significantly between the 2 groups. One patient was coinfected with anaplasmosis and had no cardiac complications.

Table 3.

Cardiovascular Disease Risk Factors, Preexisting Cardiac Conditions, and Outcomes

Variable	Patients, No. (%)a			P Valueb
	All Patients (n = 163)	Cardiac Complications
		Yes (n = 32)	No (n = 131)
Cardiovascular disease risk factors
ȃDiabetes mellitus	23 (14.1)	3 (9.4)	20 (15.3)	.57
ȃHyperlipidemia	64 (39.3)	16 (50.0)	48 (36.6)	.17
ȃHypertension	82 (50.3)	20 (62.5)	62 (47.3)	.12
ȃObesity (BMI ≥30c)	27 (16.6)	5 (15.6)	22 (16.8)	.87
Preexisting cardiac conditions
ȃCoronary artery disease	17 (10.4)	5 (15.6)	12 (9.2)	.28
ȃȃCoronary artery bypass grafting	2 (1.2)	1 (3.1)	1 (0.8)	.36
ȃȃPrior percutaneous intervention	7 (4.3)	1 (3.1)	6 (4.6)	>.99
ȃȃMyocardial infarction	5 (3.1)	0 (0.0)	(3.8)	.58
ȃHeart failure	6 (3.7)	3 (9.4)	3 (2.3)	.09
ȃCardiomyopathyd	2 (1.2)	1 (3.1)	1 (0.8)	.36
ȃArrhythmiae	10 (6.1)	3 (9.4)	7 (5.3)	.41
ȃConduction diseasef	2 (1.2)	0 (0.0)	2 (1.5)	>.99
ȃValvular diseaseg	2 (1.2)	0 (0.0)	2 (1.5)	>.99
Other comorbid conditions
ȃChronic kidney disease	8 (4.9)	0 (0.0)	8 (6.1)	.36
ȃCOPD	8 (4.9)	1 (3.1)	7 (5.3)	>.99
Complications
ȃHigh-grade parasitemia (>10%)	37 (22.7)	15 (46.9)	22 (16.8)	<.001h
ȃRBC exchange transfusion	35 (21.5)	16 (50.0)	19 (14.5)	<.001h
Outcomes
ȃLength of hospital stay, median (IQR), d	6.0 (4.0)	8.5 (7.0)	5.0 (3.0)	<.001h
ȃICU admission	56 (34.4)	25 (78.1)	31 (23.7)	<.001h
ȃLength of ICU stay, median (IQR), d	3.0 (5.0)	4.0 (5.0)	2.0 (1.0)	.01h
ȃDeath	4 (2.5)	3 (9.4)	1 (0.8)	.02h

Abbreviations: BMI, body mass index; COPD, chronic obstructive pulmonary disease; ICU, intensive care unit; IQR, median interquartile range; RBC, red blood cell.

Data represent no. (column %) unless otherwise specified; column percentages may not add up to 100% owing to rounding.

Analysis of variance was assessed using Mann-Whitney U test for continuous variables and χ² test for categorical variables; Fisher exact test was used when there were <5 samples in a given category.

BMI calculated as weight in kilograms divided by height in meters squared.

Cardiomyopathy without clinical heart failure.

Including atrial fibrillation (n = 8), atrial flutter (n = 1), and atrial tachycardia (n = 1).

Bundle-branch block.

Aortic stenosis, at least moderate to severe.

Significant at P < .05.

We investigated the possible relationship between antibiotic (especially azithromycin and quinine) use and cardiac arrhythmia. Thirteen patients had documented QTc interval prolongation on ECGs, and 2 had ventricular arrhythmias. They were given a variety of antibiotic regimens before the onset of their cardiac complications. Six patients were taking a combination of azithromycin and atovaquone, 5 were given clindamycin and quinine, and 2 were taking a combination of azithromycin, atovaquone, and clindamycin. For these patients, the maximum QTc interval recorded on ECGs ranged from 501 to 620 milliseconds. Five of the patients had also been taking prescription medications known to prolong the QT interval before admission, including amiodarone (n = 2), sotalol (n = 1), fluconazole (n = 1), sertraline (n = 1), ondansetron (n = 1), and nortriptyline (n = 1). Electrolyte disturbances were noted in 23 patients; 7 (53.8%) had hypokalemia (potassium <3.5 mmol/L), 6 (46.1%) had hypomagnesemia (magnesium <1.8 mg/dL), and 10 had hypocalcemia (calcium <7.6 mg/dL). Overlapping treatment regimens and the relatively small number of patients prevented us from drawing conclusions about a possible relationship between antibiotic use and cardiac arrhythmia.

Finally, we examined babesiosis-related risk factors for cardiac complications. The cardiac complication group had a higher percentage of patients with high-grade parasitemia (>10%) (46.9% vs 16.8%; P < .001) and lower minimum hematocrit and were more likely to have undergone RBC exchange transfusion, a treatment used for severe babesiosis (50.0% vs 14.5%; P < .001) (Table 3). The minimum hematocrit also differed between the groups (median, 23.9% vs 26.9%; P = .005), although only 2 patients had a minimum hematocrit level within the normal range. C-reactive protein (CRP) was measured in 17 patients, 1 of whom had cardiac complications and a CRP level >300 mg/L, too small a number to make any statistical inference about a possible association.

Outcome of Cardiac Complications of Babesiosis

Patients with cardiac complications had a significantly longer median (IQR) hospital stay (8.5 days [7.0]) than those without cardiac complications (8.5 [7.0] vs 5.0 [3.0] days, respectively; P < .001) (Table 3). Those in the cardiac complication group were also admitted to the ICU more frequently than those without cardiac complications (78.1% vs 23.7%, respectively; P < .001) and had significantly longer median (IQR) ICU stays (4.0 [5.0] vs 2.0 [1.0] days; P = .01).

Four of the 163 study patients died, and the mortality rate was higher in the cardiac complication group than in the group without cardiac complications (9.4% vs 0.8%, respectively; P = .02), although the deaths were not specifically attributed to cardiac issues. Patient 1 was a 77-year-old man with previous atrial fibrillation. He experienced atrial fibrillation and flutter with rapid ventricular response, QTc interval prolongation, and NSTEMI type 2 during admission. His parasitemia level peaked at 17%, and he received clindamycin plus quinine and a RBC exchange transfusion. His hospitalization course was complicated by progressively worsening acute kidney injury, metabolic acidosis, severe transaminitis, and increasing pressor requirements. He experienced shock and died 4 days after hospital admission.

Patient 2 was a 68-year-old man with no previous cardiac conditions. During his 19-day hospitalization, he experienced atrial fibrillation and atrial flutter with rapid ventricular response, new-onset heart failure with reduced ejection fraction, and NSTEMI type 2. The patient had a peak parasitemia of 4.6% and was initially treated with a course of atovaquone plus azithromycin, followed by 7 days of clindamycin plus quinine. After development of refractory ARDS, renal failure, and splenic infarct with hemoperitoneum and deep venous thrombosis, he experienced pulseless electrical activity arrest and died of refractory shock.

Patient 3 was a 55-year-old man with previous hepatitis C virus infection, cirrhosis, and asplenia but no history of cardiac disease. His hospital course was complicated by NSTEMI type 2, ARDS, septic shock, renal failure, acute liver failure, DIC, and coma. His peak parasitemia was 15.6%, and he was given an antimicrobial course of atovaquone plus azithromycin, followed by clindamycin plus quinine. He received an RBC transfusion and subsequent daily transfusions as needed but continued to have massive intravascular hemolysis and DIC, became hypotensive, and declined hemodynamically until he died after 6 days of hospitalization.

Patient 4 was a 67-year-old woman who had previous hypertension, diabetes mellitus, and alcoholic cirrhosis but no cardiac complications. She was initially given atovaquone plus azithromycin and later given clindamycin plus quinine. She had a peak parasitemia of 9.4% and received 2 RBC exchange transfusions. Severe hypotension, worsening acute kidney injury and acidosis developed, and the patient died after a 5-day hospitalization.

DISCUSSION

Cardiac complications occurred in about a fifth of patients with babesiosis who were admitted to YNHH from 2011 to 2021. The most common cardiac complications were supraventricular arrhythmia (predominantly atrial fibrillation) (10.4%), congestive heart failure (8.6%), QTc interval prolongation (8.0%), and cardiac ischemia (6.8%). Older age and high-grade parasitemia (>10%) were significantly associated with the development of cardiac complications. The median age of patients who experienced cardiac complications was higher than that of those without cardiac complications (72.5 vs 66 years, respectively). We also found that the median minimum hematocrit was lower in patients who had cardiac complications. Anemia has been shown to be a risk factor for cardiovascular disease [23] and in several studies has been associated with poorer outcomes in patients with heart failure [24].

Previously identified risk factors for cardiac complications, such as preexisting cardiac, pulmonary, or renal disease, diabetes mellitus, hyperlipidemia, hypertension, or obesity, were not associated with increased risk of cardiac complications in our cohort. The impact of cardiac complications on healthcare use was significant, with longer median length of hospital and ICU stays seen among patients with cardiac complications. Cardiac complications also significantly affect the health burden of malaria, a related intraerythrocytic piroplasm. For example, in a study of 100 patients with severe Plasmodium vivax malaria [25], 17% had cardiovascular involvement and 7% experienced congestive cardiac failure, compared with 19.6% and 8.6%, respectively, in our study.

Infection is a frequent precipitant for atrial fibrillation [26], one of the most common cardiac complications among our study patients. Several proinflammatory mediators, including CRP, interleukin 6, and tumor necrosis factor, have been linked to an increase in incidence in atrial fibrillation [27]. These and other proinflammatory mediators have been shown to be elevated during acute babesiosis, particular with severe disease [28, 29]. An insufficient number of CRP tests were obtained to evaluate any relationship with cardiac complications in our patients. All the patients who experienced atrial fibrillation were treated with rate- or rhythm-controlling agents and 4 of 10 patients with new-onset atrial fibrillation were treated with anticoagulants. Patients with infection-related atrial fibrillation have a higher rate of adverse outcomes, including recurrent atrial fibrillation and thromboembolic events [26], although we found no evidence of either of these complications in our patients.

QT interval prolongation, a measure of delayed ventricular repolarization, also was prevalent in our study patients. Excessive QT interval prolongation can increase a person’s risk of experiencing torsade de pointes, a rare but potentially lethal polymorphic ventricular tachycardia [20, 30–32]. The recommended antibiotic combinations for treatment of babesiosis are atovaquone plus azithromycin or clindamycin plus quinine. Either azithromycin or quinine may induce QT interval prolongation, even when administered for short periods of time [20, 31–35]. QT interval prolongation appears to resolve with termination of either drug, and the overall risk of torsade de pointes is low [30, 35–37]. Patients at increased risk of QTc interval prolongation include elderly women, persons with advanced heart disease, and those taking medications that prolong the QT interval or have the potential to inhibit important drug elimination mechanisms [32, 33, 37]. In the current study, all 13 patients in whom QTc interval prolongation developed had ≥1 risk factor. One patient developed torsade de pointes and required treatment with defibrillation, which successfully terminated the arrhythmia.

Heart failure was the second most common cardiac complication, including acute heart failure with both preserved and reduced ejection fraction. Of the 14 patients who experienced acutely decompensated heart failure, 11 had new diagnoses. A common theme seen in these patients was the administration of fluids, either for volume resuscitation in the setting of shock or for transfusion for anemia. While the frequency of heart failure in these patients may in part reflect the use of high-volume infusions, 6 patients were found to have a newly reduced ejection fraction during their hospital stay. Several mechanisms may explain these findings. One patient who had type 1 NSTEMI was thought to have ischemic cardiomyopathy and reduced ejection fraction. Three other patients experienced cardiac ischemia owing to supply-demand mismatch and may have had both diastolic and systolic dysfunction. It is unclear whether or not nonischemic myocardial injury may have played a role in the other patients’ heart failure. Two patients were noted to have rapid recovery of the ejection fraction within 2 weeks, with no other intervention than treatment of babesiosis, suggesting possible Babesia-induced stress-induced cardiomyopathy [18].

Cardiac ischemia was noted in 1 patient with type 1 and 10 with type 2 NSTEMI. While the precise cascade of events that precipitated the type 1 NSTEMI is unclear, there is evidence that infection and inflammation can lead to plaque disruption and thrombosis [38]. Precipitating causes of type 2 NSTEMI include severe anemia, hypoxic respiratory failure, and hypotension/shock secondary to severe babesiosis. While there are no studies describing the histopathological changes in the human heart due to babesiosis alone, a hamster Babesia model demonstrated vascular stasis and anoxic tissue injury [39]. Another B. microti hamster study revealed several histopathological changes in the heart, including myocardial fiber necrosis, infiltration of inflammatory cells, and acute myocarditis [40]. None of the patients in this study had a diagnosis of myocarditis, although a number may have had nonischemic myocardial injury. In addition, not all patients had blood tested for troponins.

Limitations of this study include the retrospective design and the lack of histopathological data and universal ECG, echocardiogram, and CRP testing that might have provided insight into the mechanisms of several cardiac complications. YNHH is a regional referral center and probably admits patients with more severe illness on average than community hospitals, although most of our patients are referred from surrounding communities.

In conclusion, cardiac complications were detected in about a fifth of 163 patients admitted to YNHH over a 10-year period for severe babesiosis. Three of 4 patients who died had cardiac complications, which contributed to death. Hospitalized patients with babesiosis should be monitored carefully for cardiac complications.

Notes

Disclaimer. The contents of this article are solely the responsibility of the authors and do not necessarily represent the official view of the National Institutes of Health.

Financial support. This work was supported by the Llura A. Gund Laboratory for Vector-borne Diseases and the Gordon and Llura Gund Foundation (grant to P. J. K.) and the National Center for Advancing Translational Science, National Institutes of Health (Clinical and Translational Science Award grant UL1 TR001863 to the Yale Center for Clinical Investigation Joint Data Analytics Team).