Left ventricular summit cryoablation via the great cardiac vein in ventricular arrhythmias treatment: a case series

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BACKGROUND

Ventricular arrhythmias are a major public health issue; they are associated with an increased risk of decompensation of chronic heart failure and are the leading cause of sudden cardiac death [1–4].

Ventricular arrhythmias are classified as ventricular premature beats and ventricular tachycardia [5]. Idiopathic ventricular premature beats account for a significant proportion of all cases of ventricular arrhythmias in the absence of structural heart disease [6]. In 80% of cases, the arrhythmogenic substrate of idiopathic ventricular extrasystoles is located in the efferent tracts of the right or left ventricle [7]. Epicardial localization of the arrhythmogenic substrate is detected in 10% of cases [8].

Pharmacological treatment aimed at reducing the prevalence of ectopic activity is characterized by limited efficacy, which makes pharmacotherapy unacceptable for patients with frequent or life-threatening ventricular arrhythmias [9]. In such cases, surgical techniques—which in most cases involve catheter-based procedures—are considered as an alternative treatment. According to R. Latchamsetty et al. [10], the success rate of radiofrequency ablation (RFA) reaches 84% when the arrhythmogenic substrate is located endocardially, particularly in the efferent tracts of the left and right ventricles. In cases of epicardial localization of the arrhythmogenic substrate, the efficacy of RFA drops to 50%, which is due to several factors: technical difficulties with access, the presence of epicardial fat, and coronary arteries in the RFA area [11]. Ensuring the safety of interventional treatment in such cases is possible through the use of alternative methods, such as cryoablation.

Currently, the choice between RFA and cryoablation is not regulated. Since the literature on the use of this technology for treating ventricular arrhythmias is limited, we present clinical observations in which cryoablation was performed on the arrhythmogenic region of the anterobasal portion of the interventricular septum via the great cardiac vein.

CASE REPORTS

Clinical Case 1

Patient Information. A 66-year-old man was admitted to the department complaining of irregular heartbeat and shortness of breath during physical exertion. In the summer of 2016, a routine examination revealed ventricular extrasystoles (15,000/day) and episodes of ventricular tachycardia. Antiarrhythmic therapy (amiodarone) was prescribed but had no significant effect.

Examination findings. Physical examination: general condition satisfactory; skin color normal; no peripheral edema. Respiratory rate 18/min; vesicular breathing; no rales. Heart sounds are muffled and rhythmic; no murmurs; ventricular rate is 66/min; blood pressure at the time of examination was 100/70 mm Hg. On palpation, the abdomen is soft and painless; the liver is palpable at the edge of the costal margin. Urination and bowel movements are normal. To rule out coronary artery disease, coronary angiography was performed: the coronary arteries are intact. Transthoracic echocardiography: systolic and diastolic cardiac function are normal. Laboratory findings: urea 5.29 mmol/L, creatinine 100 μmol/L, potassium 4.40 mmol/L. Invasive electrophysiological study: initially, cardiac endograms showed sinus rhythm, an RR interval of 850 ms, a PQ interval of 170 ms, and frequent monomorphic ventricular extrasystoles.

Treatment. A puncture and catheterization of the right femoral artery were performed. The left ventricle was mapped; no areas of earliest myocardial activation were identified. The right femoral vein was catheterized, and a 7F Freezor Xtra catheter was advanced into the right heart chambers for subsequent cryoablation. The catheter was advanced through the coronary sinus into the vena cava. The left ventricle was mapped, and the area of earliest myocardial excitation was identified at a distance of 1.5 mm in the projection of the bifurcation of the left main coronary artery (Fig. 1). The left femoral artery was punctured and catheterized via a guidewire; a Judkins catheter was advanced through its lumen and positioned in the supravalvular aorta. A cryoballoon catheter was positioned in the great cardiac vein within the zone of earliest myocardial activation against a background of ectopic activity, where cryotherapy was performed for 240 seconds at a temperature of −83°C. The ectopic activity disappeared. The changes persisted for 30 minutes. Follow-up coronary angiography revealed TIMI 3 blood flow with no signs of coronary artery stenosis (Fig. 2).

 

Fig. 1. Intraoperative 12-lead electrocardiogram (Clinical Case 1, male, 66 years old): Frequent ventricular extrasystoles are recorded against a background of sinus rhythm; a pseudo-delta wave is present in V1–V3; an R wave is recorded in lead V6; a negative R wave is present in aVL; the internal deviation index is 67 ms. Activation mapping (a): presystolic activity at 45 ms. Pacing mapping (b, c): spontaneously generated (b) and paced QRS complexes are identical (the ventricular premature beat during sinus rhythm is highlighted with a red dotted line).

 

Fig. 2. Intraoperative angiography, right oblique projection with caudal angulation (clinical case 1, 66-year-old male): the distance from the endocardial electrode to the left coronary artery trunk is 1.5 mm (marked with a yellow circle).

 

Course and оutcomes. During 24 months of follow-up, no ventricular ectopic activity was recorded in the patient following discontinuation of antiarrhythmic therapy.

Clinical Case 2

Patient Information. A 62-year-old man presented with complaints of irregular heartbeat and shortness of breath. Long-term electrocardiogram monitoring revealed frequent polymorphic ventricular extrasystoles.

In 2017 and 2018, RFA procedures were performed; early arrhythmia recurrences were noted following the procedures. Drug therapy (lappaconitine hydrobromide, sotalol, propafenone) was ineffective. The patient has hypertension, coronary artery atherosclerosis, and grade I obesity (body weight 85 kg, height 163 cm, body mass index 31.9 kg/m²).

Examination findings. On physical examination, the patient’s general condition is satisfactory. Consciousness is clear. The skin is of normal color and moisture. The mucous membranes and sclera are of normal color, without edema. Respiratory system: vesicular breathing, no wheezing. Cardiovascular system: heart sounds are clear, rhythm is irregular. Blood pressure 140/85 mm Hg. Pulse 75/min. The abdomen is soft and painless on palpation. Urination is normal. Echocardiography: left ventricular ejection fraction (Simpson) 62%. Left ventricular hypertrophy (concentric). Enlargement of both atria. Grade I left ventricular diastolic dysfunction. Moderate mitral and tricuspid regurgitation. Mild pulmonary hypertension, Grade I. No pericardial effusion or valvular defects.

Treatment. Invasive electrophysiological study: on the baseline electrocardiogram, RR 730 ms, PQ 130 ms, QRS 140 ms, QT 375 ms, left ventricular bi- and trigeminy, complete right bundle branch block (Fig. 3). Punctures and catheterizations of the right internal jugular vein and the left common femoral vein were performed sequentially; diagnostic electrodes were advanced into the cardiac cavity and placed in the coronary sinus and the right ventricle. During the invasive electrophysiological study, antegrade measurements showed a sinus node recovery time of 1,130 ms (corrected time of 400 ms); the Wenkebach point was 206 beats per minute, and the effective refractory period of the atrioventricular (AV) junction was shorter than that in the right atrium (230 ms); Retrograde: the Wenkebach point is >200 beats per minute, and the effective refractory period of the atrioventricular junction is <200 ms. There are no signs of longitudinal dissociation.

 

Fig. 3. Intraoperative 12-lead electrocardiogram (Clinical Case 2, male, 62 years old): frequent ventricular extrasystoles are recorded against a background of sinus rhythm. A transition zone is present in chest lead V2; a pseudo-delta wave is observed in leads V2–V6; an R wave is recorded in lead V6; a negative R wave is present in lead aVL; rS waves are recorded in lead I; and the internal deviation index is 78 ms.

 

Puncture and catheterization of the right common femoral artery were performed; the left sinus of Valsalva—the site of the earliest ventricular myocardial excitation (presystolic activity at 15 ms)—was mapped. The right common femoral vein was punctured and catheterized via a guidewire; an 8F introducer was placed, through which a catheter for radiofrequency ablation was advanced into the right heart and positioned in the coronary sinus. The coronary sinus was mapped. The area of earliest myocardial excitation (presystolic activity at 57 ms) was located in the proximal portion of the great cardiac vein (Fig. 4).

 

Fig. 4. 3D reconstruction of the coronary sinus and right atrium showing the cryocatheter on the CARTO 3 system (clinical case 2, 62-year-old male): ablation electrode in the right ventricle (1); aortic root (2); Freezor Xtra 7F cryocatheter (3); left ventricle (epicardial location of the cryodestruction site) (4). R, L—right and left sides of the heart in the frontal plane.

 

The right radial artery was punctured and catheterized via a guidewire; a 5F introducer was placed, through which a diagnostic catheter was advanced into the ascending aorta. The ostium of the left coronary artery was catheterized. Coronary angiography was performed: the ablation catheter was positioned in the vena cava 5 mm from the bifurcation of the left main coronary artery. The RFA catheter was replaced with a Freezor Xtra cryocatheter and positioned in the area of earliest ventricular activation against a background of ectopic activity. Cryoablation was performed in this zone for 240 seconds at a temperature of −83°C. The ectopic activity disappeared. The changes remained stable for 30 minutes. Follow-up coronary angiography showed TIMI 3 blood flow with no signs of coronary artery stenosis (Fig. 5).

 

Fig. 5. Intraoperative angiography, 30° left oblique projection with 30° caudal angulation (Clinical Case 2, 62-year-old male): the distance from the endocardial electrode to the left main coronary artery is 5 mm (marked with a yellow circle).

 

Course and оutcomes. During the 12-month follow-up period, no ventricular ectopic activity was recorded in the patient following the discontinuation of antiarrhythmic therapy.

DISCUSSION

When pharmacological treatment proves ineffective in eliminating ventricular ectopic activity, interventional techniques are employed, among which catheter ablation has become the most widely used [12].

To eliminate the substrate of ventricular extrasystoles in the anterobasal region of the interventricular septum, epicardial ablation via a subxyphoid approach may be required; however, the use of this approach in routine clinical practice is associated with a risk of life-threatening complications (cardiac tamponade, coronary artery injury, endocarditis, and pericarditis); their incidence reaches 8% [11, 13]. An alternative approach to the epicardial space is a catheter-based procedure via the cardiac venous system.

In a study by G.R. Matsonashvili et al. [14], transcatheter RFA via the great cardiac vein was successfully performed. The authors noted that radiofrequency ablation in this area is associated with a high risk of complications due to the proximity of the coronary arteries. A study by S.V. Korolev et al. [15] demonstrated that alcohol ablation is a viable option when RFA proves ineffective in eliminating the epicardial substrate of ventricular extrasystoles. According to the authors, the use of this technology may be limited if the arrhythmogenic substrate is located in close proximity to the coronary arteries. Z. Kis et al. [16] reported a clinical case of acute cardiac tamponade following transcatheter RFA in the coronary sinus.

It is well known that cryotechnologies are characterized by a high safety profile and the ability to perform the procedure in close proximity to a coronary artery. Cryoablation utilizes tissue cooling based on the Joule–Thomson effect: the temperature of gases decreases as they expand. Cryoablation can be divided into three main stages: the freeze-thaw cycle, inflammation, and fibrosis. During the freeze-thaw stage, low temperatures cause a slowing of metabolism in cardiomyocytes and the destruction of ion channels. During thawing, the ice formed outside the cells melts, creating an osmotic gradient that causes water to flow into the cells, leading to their swelling and rupture [17]. The effectiveness of these processes depends on the temperature and duration of exposure.

Brief cooling to -30°C causes reversible changes, allowing the cells to recover upon rewarming. This characteristic forms the basis of cryomapping— a method used to test the effects of cooling, particularly near the normal conduction system, such as at paragisial atrioventricular junctions. Prolonged exposure leads to the formation of ice crystals, causing irreversible cell damage. Crystals first form in the extracellular space at temperatures between 0 and -20°C, and then inside the cells at temperatures below -40°C. The rate and intensity of crystallization depend on temperature, cooling rate, and catheter contact with the tissue. The drop in temperature also causes vasospasm and microthrombosis, leading to ischemia. The subsequent restoration of microcirculation contributes to edema and ischemic necrosis. In the next stage, processes of apoptosis and fibrosis are activated, forming a clearly defined demarcation line [18].

In the presented clinical observations, the substrate of ventricular extrasystoles was localized in the anteroseptal region of the left ventricular outflow tract at a distance of 1.5 mm (clinical case 1) and 5 mm (clinical case 2) from the left main coronary artery; Performing transcatheter RFA was not possible due to the high risk of a fatal complication—acute occlusion of the left main coronary artery. Based on the physical principles of cryotherapy outlined above, cryocatheter ablation via the great cardiac vein was selected as the interventional treatment method. The ventricular extrasystole was successfully eliminated and did not recur during the long-term follow-up period. Cryoablation via the coronary sinus allowed for the safe elimination of this life-threatening arrhythmia.

CONCLUSION

Catheter ablation of the substrate of an epicardial ventricular premature beat located in close proximity to a coronary artery can be safely performed using cryoablation. When the focus of ventricular ectopic activity is located near the cardiac venous system, the ablation catheter can be positioned via the coronary sinus. Cryocatheter ablation of the anterobasal portion of the interventricular septum, when the arrhythmogenic substrate is epicardially located, may be considered a potential approach to the interventional treatment of epicardially located ventricular extrasystoles.

Additional information

Author contributions: I.A. Khamnagadaev, managing patient treatment, performing surgery, processing and discussing the results of the study, writing the article; S.A. Thermoses, N.G. Mokrysheva, M.V. Shestakova, V.Yu. Kalashnikov, processing and discussing the results of the study, writing the text of the article; L.A. Belousov, patient treatment, participation in the surgical process, writing the text of the article; I.L. Ilyich, I.A. Bulavina, R.S. Garipov, N.I. Tyurin, writing the text of the article, search and analytical work, preparation of illustrative materials. Thereby, all authors provided approval of the version to be published and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Consent for publication: Oral voluntary informed consent was obtained from the patients for publication of the clinical case descriptions: for Clinical Example 1, dated February 10, 2017; for Clinical Example 2, dated October 23, 2024. The scope of the data to be published was agreed upon with the patients.

Funding source: State assignment Research project No. 123021000043-0, 2023-2025.

Disclosure of interests: The authors declare that they have no competing interests.

Statement of originality: The authors did not use previously published information (text, illustrations, data) while conducting this work.

Data availability statement: All data obtained in this study are available in this article.

Generative AI: Generative AI technologies were not used for this article creation.

About the authors

Igor A. Khamnagadaev

Endocrinology Research Centre; The Russian National Research Medical University named after N.I. Pirogov

Email: i@khamnagadaev.ru
ORCID iD: 0000-0002-9247-4523
SPIN-code: 6338-4990

MD, PhD, Assistant Professor

Russian Federation, Moscow; Moscow

Nikolay I. Tyurin

Endocrinology Research Centre; Buyanov City Clinical Hospital

Author for correspondence.
Email: tyurin.nikolay@endocrincentr.ru
ORCID iD: 0000-0003-3366-368X
SPIN-code: 7650-3845

MD

Russian Federation, Moscow; Moscow

Irina A. Bulavina

Endocrinology Research Centre; Buyanov City Clinical Hospital

Email: bulavina.irina@endocrincentr.ru
ORCID iD: 0000-0002-6267-3724
SPIN-code: 1275-2773

MD

Russian Federation, Moscow; Moscow

Leonid A. Belousov

Endocrinology Research Centre

Email: 3127325@gmail.com
ORCID iD: 0000-0003-4917-1743
SPIN-code: 6468-2750

MD

Russian Federation, Moscow

Ilya L. Ilyich

Buyanov City Clinical Hospital

Email: ilyich@mail.ru
ORCID iD: 0000-0003-4169-1066
SPIN-code: 5527-4146

MD

Russian Federation, Moscow

Rustem Sh. Garipov

The Russian National Research Medical University named after N.I. Pirogov

Email: rust-garipov@yandex.ru
ORCID iD: 0000-0003-3394-326X
SPIN-code: 4738-5208

MD

Russian Federation, Moscow

Sergey A. Termosesov

The Russian National Research Medical University named after N.I. Pirogov; Buyanov City Clinical Hospital

Email: stermosesov@list.ru
ORCID iD: 0000-0003-2466-7865
SPIN-code: 5785-5776

MD

Russian Federation, Moscow; Moscow

Viktor Yu. Kalashnikov

Endocrinology Research Centre

Email: Kalashnikov.Victor@endocrincentr.ru
ORCID iD: 0000-0001-5573-0754
SPIN-code: 5342-7253

MD, PhD, Corresponding member of the Russian Academy of Sciences

Russian Federation, Moscow

Marina V. Shestakova

Endocrinology Research Centre

Email: Shestakova.Marina@endocrincentr.ru
ORCID iD: 0000-0002-5057-127X
SPIN-code: 7584-7015

MD, PhD, Professor, Academician of the Russian Academy of Sciences

Russian Federation, Moscow

Natalia G. Mokrysheva

Endocrinology Research Centre

Email: mokrisheva.natalia@endocrincentr.ru
ORCID iD: 0000-0002-9717-9742
SPIN-code: 5624-3875

MD, PhD, Professor, Academician of the Russian Academy of Sciences

Russian Federation, Moscow

References

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