Koji Takahashi, Hiromasa Nakahara, Eiji Arimitsu, Satoshi Imamine, Yoshiyasu Obata,Kimio Nakanishi, Yoshiyasu Taniguchi, Maiko Amano, Chika Omori, Takafumi Okura

1. Department of Community Emergency Medicine, Ehime University Graduate School of Medicine, Ehime, Japan; 2. Department of Cardiology, Yawatahama City General Hospital, Ehime, Japan; 3. Department of Internal Medicine, Oozu City Hospital, Ehime, Japan; 4. Department of Clinical Laboratory, Oozu City Hospital, Ehime, Japan

Registries and hospital discharge datasets of unselected patients with pulmonary embolism show 30-day all-cause mortality rates of approximately 10%.[1]Clinical findings from histories and physical examinations, such as age, systemic blood pressure, and respiratory rate at presentation, classify patients into risk classes of increasing risk of death and other adverse medical outcomes.[2]

Electrocardiography (ECG) is one of the first tests performed in the emergency department for pulmonary embolism.[3]ECG abnormalities may include sinus tachycardia alone in as many as 40% of patients with acute pulmonary embolism.[4]ECG changes indicative of right ventricular strain, such as inversion of T waves in leads V1 through V4 and incomplete or complete right bundle branch block, are usually found in severe cases of pulmonary embolism.A recent report has shown that the presence of a fragmented QRS complex seems to be a novel predictor of in-hospital adverse events and long-term allcause mortality in patients with pulmonary embolism.[5]The possible mechanisms for the fragmented QRS complex in pulmonary embolism are not fully understood but are thought to be mainly due to delayed conduction-mediated depolarization abnormalities.[3]Herein, we describe a case of acute pulmonary embolism and cardiogenic shock in a patient whose ECG showed a fragmented QRS complex with an additional R-wave (r’-wave) attenuated by a short RR interval. The dynamic changes in this patient’s fragmented QRS complex suggest an early repolarization abnormality-related phenomenon.[6-8]

A 91-year-old Japanese woman was brought by an ambulance to the Oozu City Hospital, Ehime, Japan due to unconsciousness. She had not consumed tobacco, alcohol, or illicit drugs. Her medical history included an eight-month history of heart failure with preserved left ventricular ejection fraction, for which she was prescribed 4 mg candesartan cilexetil, 12.5 mg spironolactone, 5 mg carvedilol, and 5 mg dapagliflozin propylene glycolate hydrate daily at another hospital. Subsequently, her serum potassium level increased to 6.2 mEq/L, and 10 g calcium polystyrene sulfonate daily was started. She also had a history of left-sided total hip arthroplasty and bilateral cataract surgery two years before admission. In addition, she had developed pneumonia two months ago and was admitted to another hospital for nine days during which an ECG revealed neither acute pulmonary embolism nor chronic thromboembolic pulmonary hypertension (Figure 1). Her heart failure was compensated at this point. Blood tests performed at another hospital twenty days prior to admission revealed renal impairment with hyperpotassemia, hypoalbuminemia, and mild anemia. Brain natriuretic peptide levels were slightly increased (Table 1).

Figure 1 ECG recorded two months prior at another hospital. The ECG reveals normal sinus rhythm, poor precordial R-wave progression, ST-segment depression, and QT-interval prolongation of a corrected QT-interval of 505 ms. This shows neither a suspected acute pulmonary embolism nor suspected chronic thromboembolic pulmonary hypertension. ECG: electrocardiography.

In the emergency room, the patient’s physical examination revealed a body temperature of 36.9 °C, a systemic blood pressure of 69/45 mmHg, a pulse rate of 63 beats/min, and a respiratory rate of 31 breaths/min. Her oxygen saturation was 87% in room air, which increased to 95% after 3 L/min oxygen administration through an oxygen mask was started. Her level of consciousness was in the level 3 digits of the Japan Coma Scale, and her Pulmonary Embolism Severity Index score was 231 points, which was assigned as a very high-risk class.[2]No cardiac murmurs or rales in the lung fields were audible upon auscultation. The liver was not palpable, and mild pretibial edema was observed. Blood investigations revealed elevated brain natriuretic peptide and D-dimer levels, renal impairment with hyperpotassemia, hypoalbuminemia, and mild anemia (Table 1). In addition, mild liver injury was suspected. Arterial blood gas analysis under oxygen inhalation at a rate of 3 L/min through an oxygen mask with a reservoir bag revealed respiratory and metabolic acidosis. ECG revealed suspected atrioventricular junctional rhythm, right axis deviation,and fragmented QRS complexes in leads II, III, aVF,and V1 (Figure 2). Moreover, the additional R-waves(r’-wave) of the fragmented QRS complexes in leads II and aVF were attenuated by a short RR interval (Figure 3). Echocardiography demonstrated a left ventricle with a preserved ejection fraction of 58.1%, measured using the modified Simpson’s method. The left ventricle was compressed by a dilated right ventricle with McConnell’s sign, defined as severely impaired systolic function sparing the right ventricular apex. In addition, a cord-like abnormal structure extending from the inferior vena cava, suspected to be a thrombus, was identified in the right atrium, some of which traveled back and forth between the right atrium and right ventricle, was shredded, and then flowed into the pulmonary artery (Figure 4). The tricuspid regurgitation jet gradient was 27 mmHg.

Figure 2 ECG recorded on admission. The ECG reveals suspected atrioventricular junctional rhythm, right axis deviation, and fragmented QRS complexes in leads II, III, aVF, and V1. The corrected QT-interval of 400 ms is not prolonged. The two dotted rectangles indicate the parts zoomed-in from Figure 3. ECG: electrocardiography.

Figure 3 Electrocardiograms recorded on admission showing zoom-in of leads II and aVF in Figure 2. The second peak (r’-wave) of the fragmented QRS complex in leads II and aVF is attenuated by a short RR interval (black arrows), whereas the first peak is slightly increased in height (brown arrows). The numbers indicate RR-intervals (ms).

Figure 4 Transthoracic two-dimensional echocardiograms recorded on admission. The right ventricular inflow views show the left ventricle with a preserved ejection fraction of 58.1% measured using modified Simpson’s method compressed by the dilated right ventricle with severely hypokinetic wall motion sparing the right ventricular apex, known as a McConnell’s sign. In addition, a cord-like abnormal structure is extending from the inferior vena cava, suspected to be a thrombus, and is identified in the right atrium (white arrows).The cord-like structure travels back and forth between the right atrium and the right ventricle, some of which breaks off and flows into the pulmonary artery. LV: left ventricle; RA: right atrium; RV: right ventricle.

No lower extremity venous Doppler study or computed tomographic pulmonary angiography was performed. However, based on the above findings, the patient was diagnosed with an acute pulmonary embolism due to deep vein thrombosis with cardiogenic shock. Intravenous unfractionated heparin and noradrenalin were continuously administered, but the patient progressed to hepatic and renal dysfunction (Table 1) and died 12 h after admission. Autopsy was not performed.

Table 1 The patient’s blood test result.

In our patient with acute pulmonary embolism leading to cardiogenic shock, an additional R-wave (r’-wave) of the fragmented QRS complex was attenuated by a short RR interval, suggesting that a fragmented QRS complex could be due to an early repolarization abnormality.

A fragmented QRS complex in pulmonary embolism has only recently been reported. Cetin,et al.[5]defined a fragmented QRS complex by the presence of various RSR’ patterns with or without a Q-wave, inclu-ding an additional R-wave (that is, R＇), notching of the R-wave, and notching of the downstroke or upstroke of the S-wave in more than two contiguous leads representing anterior, inferior, or lateral myocardial segments.[9]Thus, a part of the fragmented QRS complex could qualify for the definition of a J-wave regarded as an end-QRS notch occurring on the final 50% of the downslope of an R-wave.[10]The presence of a fragmented QRS complex on a routine 12-lead ECG, which occurs as a result of heterogeneous myocardial activation due to myocardial ischemia, scarring, and/or fibrosis, has become a marker of depolarization abnormalities.[11]Fragmented QRS complexes have been investigated as a possible new tool in the identification of high-risk subjects with a variety of cardiovascular pathologies, such as coronary artery disease, cardiomyopathy, and Brugada syndrome. In addition, they have been reported in almost 20% of patients with cardiogenic shock and pulmonary embolism compared to 8% of patients with pulmonary embolism and no cardiogenic shock, and hence,they were found to be an independent predictor of cardiogenic shock.[12]The possible mechanisms for the fragmented QRS complexes in pulmonary embolism,although not fully understood, include an acutely elevated right ventricular pressure leading to impairmentof right ventricular myocardial activation and delayed conduction.[3]Furthermore, other potential mechanisms may involve impaired perfusion in the left ventricle caused by right ventricular dysfunction, leading to a decrease in the preload of the left ventricle.In addition, myocardial ischemia in both the right and left ventricles could be exaggerated by pulmonary embolism-associated mediators such as catecholamines.[5]

Regarding J-waves, two distinct patterns of different rate-dependent responses were observed. That is, tachycardia (bradycardia)-dependent augmentation (attenuation) or tachycardia (bradycardia)-dependent attenuation (augmentation) in the amplitude of Jwaves and the end-QRS notch. The J-wave augmented by a short RR interval, such as premature atrial contraction, is thought to be a delayed conduction-mediated depolarization abnormality.[7,13]In contrast, J-wave attenuation by a short RR interval is a characteristic finding of a transient outward current-mediated early repolarization abnormality.[6,14]In this setting, a possible mechanism is thought to be the reduced availability of transient outward current due to slow recovery from inactivation.[15]In addition, a stable J-wave pattern, unaffected by the RR interval, is likely caused by a depolarization abnormality with potential exacerbation at short cycle lengths, and vice versa for early repolarization.[8]In our patient, an additional Rwave (r’-wave) of the fragmented QRS complex was clearly attenuated by a short RR interval, although the reason for this is unknown. Our case was not one with a J-wave by definition.[10]However, we speculate that the same phenomenon occurred as a J-wave lowered in height by the short RR interval, a reverse aspect of pause-dependent augmentation of J-waves. In fact, Jwaves that increase in height under certain conditions do not meet the definition of J-waves and are often considered fragmentations.[6-8,15]Dynamic J-wave changes are thought to increase the risk of lethal ventricular tachyarrhythmias.

In conclusion, this case of acute pulmonary embolism complicated by cardiogenic shock shows fragmentation of the QRS complex suggestive of a transient outward current-mediated early repolarization abnormality, although no ventricular fibrillation was found. Hence, in this setting, treatment for lethal ventricular arrhythmias, in addition to antithrombotic treatment for pulmonary embolism, may be necessary.

ACKNOWLEDGMENTS

All authors had no conflicts of interest to disclose.