The Incidence and Impact of Permanent Right Ventricular Infarction on Left Ventricular Infarct Size in Patients With Inferior ST-Segment Elevation Myocardial Infarction

Mounting evidence shows that right ventricle (RV) function carries independent prognostic influence in various disease states. This study aimed to investigate the incidence and impact of permanent RV infarction in patients with inferior ST-segment elevation myocardial infarction (STEMI) and culprit lesion in the right coronary artery (RCA). In this substudy of the DANAMI-3 (DANish Study of Optimal Acute Treatment of Patients with ST-segment Elevation Myocardial Infarction) trial, cardiac magnetic resonance was performed in 291 patients at day 1 and follow-up 3 months after primary percutaneous coronary intervention of 674 patients with STEMI with the culprit lesion in the RCA. Final infarct was assessed using late gadolinium enhancement on cardiac magnetic resonance at 3 months. Patients with permanent RV infarction (20%) had lower ventricular function at follow-up; RV ejection fraction (EF) 47% ±6 versus 50% ± 5 (p <0.005) and left ventricular (LV) EF 56% ± 8 versus 60% ± 9 (p <0.006). Furthermore, patients with permanent RV infarction had a higher incidence of microvascular obstruction 39 (67%) versus 81 (39%) (p <0.001), larger final LV infarct size 16% ±8 versus 10% ± 8 (p <0.001) and larger LV area at risk 33% ± 10 versus 29% ± 9 (p <0.001). Permanent RV infarction was an independent predictor of final LV infarct size (p <0.001) but was not associated with LVEF (β = −0.0; p = 0.13) in multivariable analyses. In conclusion, permanent RV infarction was seen in 20% of patients with inferior STEMI and culprit lesion in RCA and independently predicted final LV infarct size. However, permanent RV infarction did not predict overall LV function.LGE was used to detect infarct location and quantify infarct size.17Kim RJ Fieno DS Parrish TB Harris K Chen EL Simonetti O Bundy J Finn JP Klocke FJ Judd RM. Relationship of MRI delayed contrast enhancement to irreversible injury, infarct age, and contractile function.Circulation. 1999; 100: 1992-2002Crossref PubMed Scopus (2134) Google Scholar LGE in RV free wall on follow-up CMR was considered as permanent infarction. LGE images were obtained 10 minutes after intravenous injection of 0.1-mmol/kg body weight of gadolinium-based contrast (Gadovist; Bayer Schering, Berlin, Germany) using an electrocardiogram (ECG)-triggered inversion-recovery sequence. The inversion time was adjusted to null the signal from the normal myocardium. Short-axis images were acquired from the atrioventricular plane to the apex with adjacent 8-mm slices. The remaining protocol has been described previously.16Nepper-Christensen L Lønborg J Ahtarovski KA Høfsten DE Kyhl K Ghotbi AA Schoos MM Göransson C Bertelsen L Køber L Helqvist S Pedersen F Saünamaki K Jørgensen E Kelbæk H Holmvang L Vejlstrup N Engstrøm T. Left ventricular hypertrophy is associated with increased infarct size and decreased myocardial salvage in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention.J Am Heart Assoc. 2017; 6Crossref PubMed Scopus (36) Google Scholar Mounting evidence shows that right ventricle (RV) function carries independent prognostic influence in various disease states. This study aimed to investigate the incidence and impact of permanent RV infarction in patients with inferior ST-segment elevation myocardial infarction (STEMI) and culprit lesion in the right coronary artery (RCA). In this substudy of the DANAMI-3 (DANish Study of Optimal Acute Treatment of Patients with ST-segment Elevation Myocardial Infarction) trial, cardiac magnetic resonance was performed in 291 patients at day 1 and follow-up 3 months after primary percutaneous coronary intervention of 674 patients with STEMI with the culprit lesion in the RCA. Final infarct was assessed using late gadolinium enhancement on cardiac magnetic resonance at 3 months. Patients with permanent RV infarction (20%) had lower ventricular function at follow-up; RV ejection fraction (EF) 47% ±6 versus 50% ± 5 (p <0.005) and left ventricular (LV) EF 56% ± 8 versus 60% ± 9 (p <0.006). Furthermore, patients with permanent RV infarction had a higher incidence of microvascular obstruction 39 (67%) versus 81 (39%) (p <0.001), larger final LV infarct size 16% ±8 versus 10% ± 8 (p <0.001) and larger LV area at risk 33% ± 10 versus 29% ± 9 (p <0.001). Permanent RV infarction was an independent predictor of final LV infarct size (p <0.001) but was not associated with LVEF (β = −0.0; p = 0.13) in multivariable analyses. In conclusion, permanent RV infarction was seen in 20% of patients with inferior STEMI and culprit lesion in RCA and independently predicted final LV infarct size. However, permanent RV infarction did not predict overall LV function. LGE was used to detect infarct location and quantify infarct size.17Kim RJ Fieno DS Parrish TB Harris K Chen EL Simonetti O Bundy J Finn JP Klocke FJ Judd RM. Relationship of MRI delayed contrast enhancement to irreversible injury, infarct age, and contractile function.Circulation. 1999; 100: 1992-2002Crossref PubMed Scopus (2134) Google Scholar LGE in RV free wall on follow-up CMR was considered as permanent infarction. LGE images were obtained 10 minutes after intravenous injection of 0.1-mmol/kg body weight of gadolinium-based contrast (Gadovist; Bayer Schering, Berlin, Germany) using an electrocardiogram (ECG)-triggered inversion-recovery sequence. The inversion time was adjusted to null the signal from the normal myocardium. Short-axis images were acquired from the atrioventricular plane to the apex with adjacent 8-mm slices. The remaining protocol has been described previously.16Nepper-Christensen L Lønborg J Ahtarovski KA Høfsten DE Kyhl K Ghotbi AA Schoos MM Göransson C Bertelsen L Køber L Helqvist S Pedersen F Saünamaki K Jørgensen E Kelbæk H Holmvang L Vejlstrup N Engstrøm T. Left ventricular hypertrophy is associated with increased infarct size and decreased myocardial salvage in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention.J Am Heart Assoc. 2017; 6Crossref PubMed Scopus (36) Google Scholar First-line treatment of ST-segment elevation myocardial infarction (STEMI) is timely executed primary percutaneous coronary intervention (PCI). Clinical outcomes and prognosis in patients with STEMI have improved significantly since the implementation of primary PCI.1Ibánez B James S Agewall S Antunes MJ Bucciarelli-Ducci C Bueno H Caforio ALP Crea F Goudevenos JA Halvorsen S Hindricks G Kastrati A Lenzen MJ Prescott E Roffi M Valgimigli M Varenhorst C Vranckx P Widimský P. 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation.Rev Esp Cardiol (Engl Ed). 2017; 70: 1082PubMed Google Scholar However, the location of the culprit lesion is a major determinant of the clinical course and outcome.2Harjai KJ Mehta RH Stone GW Boura JA Grines L Brodie BR Cox DA O'Neill WW Grines CL Primary Angioplasty In Myocardial Infarction (PAMI) Investigators. Does proximal location of culprit lesion confer worse prognosis in patients undergoing primary percutaneous coronary intervention for ST-elevation myocardial infarction?.J Interv Cardiol. 2006; 19: 285-294Crossref PubMed Scopus (30) Google Scholar, 3Kandzari DE Tcheng JE Gersh BJ Cox DA Stuckey T Turco M Mehran R Garcia E Zimetbaum P McGlaughlin MG Lansky AJ Costantini CO Grines CL Stone GW Investigators CADILLAC Relationship between infarct artery location, epicardial flow, and myocardial perfusion after primary percutaneous revascularization in acute myocardial infarction.Am Heart J. 2006; 151: 1288-1295Crossref PubMed Scopus (48) Google Scholar, 4Nienhuis MB Ottervanger JP Dambrink JH de Boer MJ Hoorntje JC Gosselink AT Suryapranata H van't Hof AW. Comparative predictive value of infarct location, peak CK, and ejection fraction after primary PCI for ST-elevation myocardial infarction.Coron Artery Dis. 2009; 20: 9-14Crossref PubMed Scopus (24) Google Scholar It is well known that patients with hemodynamically significant right ventricle (RV) infarction have a worse prognosis in the acute phase, with increased risk of major complications compared with patients without RV infarct.5Mehta SR Eikelboom JW Natarajan MK Diaz R Yi C Gibbons RJ Yusuf S. Impact of right ventricular involvement on mortality and morbidity in patients with inferior myocardial infarction.J Am Coll Cardiol. 2001; 37: 37-43Crossref PubMed Scopus (319) Google Scholar, 6Inohara T Kohsaka S Fukuda K Menon V. The challenges in the management of right ventricular infarction.Eur Heart J Acute Cardiovasc Care. 2013; 2: 226-234Crossref PubMed Scopus (37) Google Scholar, 7Sewdarsen M Vythilingum S Moodley T. Incidence and bedside diagnosis of haemodynamically significant right ventricular infarction.S Afr Med J. 1988; 73: 9-11PubMed Google Scholar In approximately 50% of patients with STEMI, the culprit lesion is located in the right coronary artery (RCA) and can cause an inferior STEMI.8Warner MJ Tivakaran VS. Inferior Myocardial Infarction. Treasure Island. StatPearls Publishing, 2020Google Scholar As the RCA supplies approximately 1/3 of the posterior interventricular septum, the inferior portion of the left ventricular (LV), the sinus node, and the atrioventricular node and has branches supplying the RV, patients with inferior STEMI typically experience bradycardia and RV failure.9Ogobuiro I Wehrle CJ Anatomy Tuma F. Heart Coronary Arteries. Treasure Island.Thorax. 2020; Google Scholar Through decades, the function of the RV has been neglected in comparison with the LV, but the role of RV in prognosis and functional status is now being recognized.10Sanz J Sánchez-Quintana D Bossone E Bogaard HJ Naeije R. Anatomy, function, and dysfunction of the right ventricle: JACC State-of-the-art Review.J Am Coll Cardiol. 2019; 73: 1463-1482Crossref PubMed Scopus (295) Google Scholar Cardiac magnetic resonance (CMR) studies show that the presence of edema, myocardial infarction measured as late gadolinium enhancement (LGE), microvascular obstruction (MVO), and impaired wall motion is associated with poor prognosis.11de Waha S Patel MR Granger CB Ohman EM Maehara A Eitel I Ben-Yehuda O Jenkins P Thiele H Stone GW. Relationship between microvascular obstruction and adverse events following primary percutaneous coronary intervention for ST-segment elevation myocardial infarction: an individual patient data pooled analysis from seven randomized trials.Eur Heart J. 2017; 38: 3502-3510Crossref PubMed Scopus (219) Google Scholar,12Stone GW Selker HP Thiele H Patel MR Udelson JE Ohman EM Maehara A Eitel I Granger CB Jenkins PL Nichols M Ben-Yehuda O. Relationship between infarct size and outcomes following primary PCI: patient-level analysis from 10 randomized trials.J Am Coll Cardiol. 2016; 67: 1674-1683Crossref PubMed Scopus (376) Google Scholar However, whether the presence of RV infarction impacts LV infarct size and function independently or whether it is merely an indication of a large myocardial infarct per se is unknown. Thus, the purposes of this study are first, to investigate the incidence of permanent RV infarction in patients with a culprit lesion in RCA using CMR. Second, to clarify whether the pathophysiologic role of permanent RV infarction in patients with inferior STEMI and culprit lesion in RCA is a direct engagement in large infarcts or alternatively independently affects LV infarct development. This is a substudy of the DANAMI-3 (DANish Study of Optimal Acute Treatment of Patients with ST-segment Elevation Myocardial Infarction) trial.13Engstrøm T Kelbæk H Helqvist S Høfsten DE Kløvgaard L Holmvang L Jørgensen E Pedersen F Saunamäki K Clemmensen P De Backer O Ravkilde J Tilsted HH Villadsen AB Aarøe J Jensen SE Raungaard B Køber L DANAMI-3—PRIMULTI Investigators. Complete revascularisation versus treatment of the culprit lesion only in patients with ST-segment elevation myocardial infarction and multivessel disease (DANAMI-3—PRIMULTI): an open-label, randomised controlled trial.Lancet. 2015; 386: 665-671Abstract Full Text Full Text PDF PubMed Scopus (651) Google Scholar, 14Engstrøm T Kelbæk H Helqvist S Høfsten DE Kløvgaard L Clemmensen P Holmvang L Jørgensen E Pedersen F Saunamaki K Ravkilde J Tilsted HH Villadsen A Aarøe J Jensen SE Raungaard B Bøtker HE Terkelsen CJ Maeng M Kaltoft A Krusell LR Jensen LO Veien KT Kofoed KF Torp-Pedersen C Kyhl K Nepper-Christensen L Treiman M Vejlstrup N Ahtarovski K Lønborg J Køber L Third Danish Study of Optimal Acute Treatment of Patients With ST-Elevation Myocardial Infarction–Ischemic Postconditioning (DANAMI-3–iPOST) Investigators. Effect of ischemic postconditioning during primary percutaneous coronary intervention for patients with ST-segment elevation myocardial infarction: a randomized clinical trial.JAMA Cardiol. 2017; 2: 490-497Crossref PubMed Scopus (102) Google Scholar, 15Kelbæk H Høfsten DE Køber L Helqvist S Kløvgaard L Holmvang L Jørgensen E Pedersen F Saunamäki K De Backer O Bang LE Kofoed KF Lønborg J Ahtarovski K Vejlstrup N Bøtker HE Terkelsen CJ Christiansen EH Ravkilde J Tilsted HH Villadsen AB Aarøe J Jensen SE Raungaard B Jensen LO Clemmensen P Grande P Madsen JK Torp-Pedersen C Engstrøm T. Deferred versus conventional stent implantation in patients with ST-segment elevation myocardial infarction (DANAMI 3-DEFER): an open-label, randomised controlled trial.Lancet. 2016; 387: 2199-2206Abstract Full Text Full Text PDF PubMed Scopus (138) Google Scholar This CMR substudy included data obtained at 1 of 4 participating centers of DANAMI-3 (Rigshospitalet, Copenhagen University Hospital).16Nepper-Christensen L Lønborg J Ahtarovski KA Høfsten DE Kyhl K Ghotbi AA Schoos MM Göransson C Bertelsen L Køber L Helqvist S Pedersen F Saünamaki K Jørgensen E Kelbæk H Holmvang L Vejlstrup N Engstrøm T. Left ventricular hypertrophy is associated with increased infarct size and decreased myocardial salvage in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention.J Am Heart Assoc. 2017; 6Crossref PubMed Scopus (36) Google Scholar Patients were qualified if they met the following criteria: ≥18 years, acute onset of chest pain of <12 hours’ duration, ST-segment elevation ≥0.1 mV in ≥2 contiguous leads, or documented newly developed left bundle branch block, culprit lesion in RCA, and having follow-up CMR. Patients with contradictions for CMR were excluded. Contraindications included claustrophobia, severely reduced kidney function, infarction in the of the and in the DANAMI-3 The was performed in with the of A and an the study protocol of the The was at CMR was performed during at day 1 1 to after primary and follow-up CMR was performed at day to after primary CMR was obtained on a and Germany) using a body were in images were used in the of RV at and at and follow-up CMR. fraction (EF) was from and J DA J MG RJ F S and in magnetic resonance for of on Cardiovasc 2020; PubMed Scopus Google Scholar The of the RV was In the of 50% of RV was excluded. LV were obtained using the and epicardial and were included in the LV CMR with were excluded. LGE is the for acute and myocardial A magnetic resonance in patients with myocardial infarction: and Am Coll Cardiol. 2009; PubMed Scopus Google A H I J R magnetic resonance of right ventricular infarction.J Am Coll Cardiol. 2006; PubMed Scopus Google Scholar LGE images were used to LV infarction and as L Lønborg J Ahtarovski KA Høfsten DE Kyhl K Ghotbi AA Schoos MM Göransson C Bertelsen L Køber L Helqvist S Pedersen F Saünamaki K Jørgensen E Kelbæk H Holmvang L Vejlstrup N Engstrøm T. Left ventricular hypertrophy is associated with increased infarct size and decreased myocardial salvage in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention.J Am Heart Assoc. 2017; 6Crossref PubMed Scopus (36) Google C Ahtarovski KA Kyhl K Lønborg J Nepper-Christensen L Bertelsen L Ghotbi AA Schoos MM Køber L Høfsten D Helqvist S Kelbæk H Engstrøm T Vejlstrup of the myocardial area at magnetic resonance with Heart J Cardiovasc 2019; 20: PubMed Scopus Google Scholar RV infarction was considered if signal of was in the RV wall and if the was O MB HP JW the of in the of infarct size and myocardial using delayed Cardiovasc PubMed Scopus Google Scholar Permanent RV infarction was as RV LGE on follow-up CMR. The epicardial and were The interventricular was from the of the RV wall size was in and of RV Patients were on the presence or of RV infarction on follow-up LGE of RV infarct was performed in 10 patients with RV infarction and as ± of ± LGE CMR area in the posterior wall of RV RV infarction. of epicardial and of area in the posterior wall of images were used to LV area at risk as Furthermore, LV infarct size and were used to the myocardial salvage using the infarct are as and compared using or are as ± if and as if for was using a a if in The and were used for normal and were on Furthermore, to the between the presence of permanent RV infarction and final LV infarct size and LV function, an analysis of was and adjusted for in myocardial infarction during age, LV and having LGE RV infarction at A p = was considered significant for analyses. were in A of 291 patients with RCA infarction had a follow-up CMR of patients (20%) had permanent RV infarction. patients were to and have acute compared with patients without permanent RV infarction Furthermore, peak were as in patients with permanent RV infarction compared with patients without permanent RV infarction and in patients with and without a permanent right ventricular infarction at RV = RV = of at during I at I in culprit lesion 1 in culprit lesion 1 lesion in RCA CMR at = acute myocardial = body = coronary artery = coronary artery CMR = magnetic = PCI = percutaneous coronary RCA = right coronary RV = right = in myocardial infarction. in a = acute myocardial = body = coronary artery = coronary artery CMR = magnetic = PCI = percutaneous coronary RCA = right coronary RV = right = in myocardial infarction. patients developed permanent RV infarction had lower right ventricular EF and left ventricular EF and increased RV and LV infarct size and LV were larger in patients developed permanent RV infarction in patients and was seen magnetic resonance in patients with and without permanent right ventricular RV infarction = RV infarction = CMR RV RV RV infarct size RV infarction at LV LV LVEF LV infarct size obstruction in LV, obstruction LV CMR RV RV RV infarct size LV LV LVEF LV infarct size = area at CMR = magnetic = = LV = left LVEF = left ventricular ejection = myocardial salvage RV = right = right ventricular ejection in a = area at CMR = magnetic = = LV = left LVEF = left ventricular ejection = myocardial salvage RV = right = right ventricular ejection Final LV infarct size was larger in patients with permanent RV infarction in patients and myocardial salvage was higher in patients without permanent RV infarction in patients with permanent RV infarction. patients with permanent RV infarction had lower and and for RV and LV were increased in patients with permanent RV infarction in patients without permanent RV infarction Permanent RV infarction was significantly associated with LV infarct size at after for and LV in a multivariable analysis significant of increased LV infarct size at follow-up were and However, was between permanent RV infarction and LVEF at follow-up of LVEF at follow-up were during and of left ventricular infarct size at in culprit lesion during area at risk RV = LV = left PCI = percutaneous coronary RV = right = in myocardial infarction. in a of left ventricular ejection fraction at in culprit lesion during area at risk RV = LV = left LVEF = left ventricular ejection PCI = percutaneous coronary RV = right = in myocardial infarction. in a = LV = left PCI = percutaneous coronary RV = right = in myocardial infarction. = LV = left LVEF = left ventricular ejection PCI = percutaneous coronary RV = right = in myocardial infarction. In patients with the culprit in RCA and inferior STEMI, 1 in 5 had evidence of permanent RV infarction CMR. Patients with permanent RV infarction were larger LV infarct size and myocardial dysfunction of the RV and Permanent RV infarction was an independent predictor of final LV infarct and this on LV infarct size is a of the decreased RV function an indication of a large RV infarction is at in patients from coronary E ventricular infarction: size and in coronary a study from a coronary Am Coll Cardiol. PubMed Scopus Google Scholar are not of a STEMI of the CMR studies of RV infarcts that RV infarction were on CMR on or However, the study was a study and only included A H I J R magnetic resonance of right ventricular infarction.J Am Coll Cardiol. 2006; PubMed Scopus Google Scholar on and of RV infarction are and a of A CMR study as an incidence of permanent RV infarction after STEMI, in with M J G R I M E C M L S J. ventricular ischemic in patients with acute ST-segment elevation myocardial infarction: with magnetic PubMed Scopus Google Scholar in a large CMR M C J J L de Waha S S Eitel I M Thiele H ventricular in ST-elevation myocardial infarction: risk of wall edema, and cardiac magnetic Cardiovasc PubMed Scopus Google Scholar a incidence of RV infarction after RV infarction was only on impaired wall motion and are M J G R I M E C M L S J. ventricular ischemic in patients with acute ST-segment elevation myocardial infarction: with magnetic PubMed Scopus Google Scholar that patients with RV infarction had lower RV function at follow-up compared with patients with In an improved RV function from to follow-up was in patients with RV and permanent M J G R I M E C M L S J. ventricular ischemic in patients with acute ST-segment elevation myocardial infarction: with magnetic PubMed Scopus Google Scholar as in In contrast to M C J J L de Waha S S Eitel I M Thiele H ventricular in ST-elevation myocardial infarction: risk of wall edema, and cardiac magnetic Cardiovasc PubMed Scopus Google Scholar that RV myocardial poor flow, and were independently associated with RV infarction after Furthermore, they did not a in LV infarct or between patients with or without RV infarction. on CMR in the acute after STEMI and impaired wall motion and edema, in contrast to on acute and follow-up LGE the that the presence of permanent RV infarction was associated with larger final infarct size and of are to poor prognosis.11de Waha S Patel MR Granger CB Ohman EM Maehara A Eitel I Ben-Yehuda O Jenkins P Thiele H Stone GW. Relationship between microvascular obstruction and adverse events following primary percutaneous coronary intervention for ST-segment elevation myocardial infarction: an individual patient data pooled analysis from seven randomized trials.Eur Heart J. 2017; 38: 3502-3510Crossref PubMed Scopus (219) Google Scholar,12Stone GW Selker HP Thiele H Patel MR Udelson JE Ohman EM Maehara A Eitel I Granger CB Jenkins PL Nichols M Ben-Yehuda O. Relationship between infarct size and outcomes following primary PCI: patient-level analysis from 10 randomized trials.J Am Coll Cardiol. 2016; 67: 1674-1683Crossref PubMed Scopus (376) Google Scholar with CMR studies have that RV infarction is significantly associated with major adverse cardiac M C J J L de Waha S S Eitel I M Thiele H ventricular in ST-elevation myocardial infarction: risk of wall edema, and cardiac magnetic Cardiovasc PubMed Scopus Google CJ M P T O. ventricular involvement in acute left ventricular myocardial infarction: prognostic of MRI Am J PubMed Scopus Google Scholar and that approximately 50% of patients experience a major adverse cardiac during a This that patients with RV involvement a The independent between permanent RV infarction and LV infarct size the reduced RV function during that LV infarct However, permanent RV infarction was not an independent predictor of for this that permanent RV infarction to in RV function not predicted It is well known that EF is not a of function of influence on and fraction and JACC State-of-the-art Review.J Am Coll Cardiol. PubMed Scopus Google Scholar are 3 study RV were performed an was not to the of RV infarction. Second, of the RV of RV infarct size is of the compared with the LV This to of the RV infarct size. only patients with a follow-up CMR were and patients of clinical were excluded. the incidence of permanent RV infarction in an In conclusion, the incidence of permanent RV infarction was 20% in patients with inferior STEMI and culprit in RCA. Patients with permanent RV infarction were larger LV infarct increased and lower LV and RV function patients The presence of permanent RV infarction was independently associated with final LV infarct size but not LV function. This that the of permanent RV infarction on LV infarct size is not only an indication of a large infarct LV and RV per se but that RV infarction affects LV infarct The have of to