Ticagrelor alone versus ticagrelor plus aspirin from month 1 to month 12 after percutaneous coronary intervention in patients with acute coronary syndromes (ULTIMATE-DAPT): a randomised, placebo-controlled, double-blind clinical trial.

BACKGROUND: Following percutaneous coronary intervention with stent placement to treat acute coronary syndromes, international clinical guidelines generally recommend dual antiplatelet therapy with aspirin plus a P2Y12 receptor inhibitor for 12 months to prevent myocardial infarction and stent thrombosis. However, data on single antiplatelet therapy with a potent P2Y12 inhibitor earlier than 12 months after percutaneous coronary intervention for patients with an acute coronary syndrome are scarce. The aim of this trial was to assess whether the use of ticagrelor alone, compared with ticagrelor plus aspirin, could reduce the incidence of clinically relevant bleeding events without an accompanying increase in major adverse cardiovascular or cerebrovascular events (MACCE). METHODS: In this randomised, placebo-controlled, double-blind clinical trial, patients aged 18 years or older with an acute coronary syndrome who completed the IVUS-ACS study and who had no major ischaemic or bleeding events after 1-month treatment with dual antiplatelet therapy were randomly assigned to receive oral ticagrelor (90 mg twice daily) plus oral aspirin (100 mg once daily) or oral ticagrelor (90 mg twice daily) plus a matching oral placebo, beginning 1 month and ending at 12 months after percutaneous coronary intervention (11 months in total). Recruitment took place at 58 centres in China, Italy, Pakistan, and the UK. Patients were required to remain event-free for 1 month on dual antiplatelet therapy following percutaneous coronary intervention with contemporary drug-eluting stents. Randomisation was done using a web-based system, stratified by acute coronary syndrome type, diabetes, IVUS-ACS randomisation, and site, using dynamic minimisation. The primary superiority endpoint was clinically relevant bleeding (Bleeding Academic Research Consortium [known as BARC] types 2, 3, or 5). The primary non-inferiority endpoint was MACCE (defined as the composite of cardiac death, myocardial infarction, ischaemic stroke, definite stent thrombosis, or clinically driven target vessel revascularisation), with an expected event rate of 6·2% in the ticagrelor plus aspirin group and an absolute non-inferiority margin of 2·5 percentage points between 1 month and 12 months after percutaneous coronary intervention. The two co-primary endpoints were tested sequentially; the primary superiority endpoint had to be met for hypothesis testing of the MACCE outcome to proceed. All principal analyses were assessed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT03971500, and is completed. FINDINGS: Between Sept 21, 2019, and Oct 27, 2022, 3400 (97·0%) of the 3505 participants in the IVUS-ACS study were randomly assigned (1700 patients to ticagrelor plus aspirin and 1700 patients to ticagrelor plus placebo). 12-month follow-up was completed by 3399 (>99·9%) patients. Between month 1 and month 12 after percutaneous coronary intervention, clinically relevant bleeding occurred in 35 patients (2·1%) in the ticagrelor plus placebo group and in 78 patients (4·6%) in the ticagrelor plus aspirin group (hazard ratio [HR] 0·45 [95% CI 0·30 to 0·66]; p<0·0001). MACCE occurred in 61 patients (3·6%) in the ticagrelor plus placebo group and in 63 patients (3·7%) in the ticagrelor plus aspirin group (absolute difference -0·1% [95% CI -1·4% to 1·2%]; HR 0·98 [95% CI 0·69 to 1·39]; pnon-inferiority<0·0001, psuperiority=0·89). INTERPRETATION: In patients with an acute coronary syndrome who had percutaneous coronary intervention with contemporary drug-eluting stents and remained event-free for 1 month on dual antiplatelet therapy, treatment with ticagrelor alone between month 1 and month 12 after the intervention resulted in a lower rate of clinically relevant bleeding and a similar rate of MACCE compared with ticagrelor plus aspirin. Along with the results from previous studies, these findings show that most patients in this population can benefit from superior clinical outcomes with aspirin discontinuation and maintenance on ticagrelor monotherapy after 1 month of dual antiplatelet therapy. FUNDING: The Chinese Society of Cardiology, the National Natural Scientific Foundation of China, and the Jiangsu Provincial & Nanjing Municipal Clinical Trial Project. TRANSLATION: For the Mandarin translation of the abstract see Supplementary Materials section.

Intravascular ultrasound-guided versus angiography-guided percutaneous coronary intervention in acute coronary syndromes (IVUS-ACS): a two-stage, multicentre, randomised trial.

BACKGROUND: Intravascular ultrasound-guided percutaneous coronary intervention has been shown to result in superior clinical outcomes compared with angiography-guided percutaneous coronary intervention. However, insufficient data are available concerning the advantages of intravascular ultrasound guidance for patients with an acute coronary syndrome. This trial aimed to investigate whether the use of intravascular ultrasound guidance, as compared with angiography guidance, improves the outcomes of percutaneous coronary intervention with contemporary drug-eluting stents in patients presenting with an acute coronary syndrome. METHODS: In this two-stage, multicentre, randomised trial, patients aged 18 years or older and presenting with an acute coronary syndrome at 58 centres in China, Italy, Pakistan, and the UK were randomly assigned to intravascular ultrasound-guided percutaneous coronary intervention or angiography-guided percutaneous coronary intervention. Patients, follow-up health-care providers, and assessors were masked to random assignment; however, staff in the catheterisation laboratory were not. The primary endpoint was target vessel failure, a composite of cardiac death, target vessel myocardial infarction, or clinically driven target vessel revascularisation at 1 year after randomisation. This trial is registered at ClinicalTrials.gov, NCT03971500, and is completed. FINDINGS: Between Aug 20, 2019 and Oct 27, 2022, 3505 patients with an acute coronary syndrome were randomly assigned to intravascular ultrasound-guided percutaneous coronary intervention (n=1753) or angiography-guided percutaneous coronary intervention (n=1752). 1-year follow-up was completed in 3504 (>99·9%) patients. The primary endpoint occurred in 70 patients in the intravascular ultrasound group and 128 patients in the angiography group (Kaplan-Meier rate 4·0% vs 7·3%; hazard ratio 0·55 [95% CI 0·41-0·74]; p=0·0001), driven by reductions in target vessel myocardial infarction or target vessel revascularisation. There were no significant differences in all-cause death or stent thrombosis between groups. Safety endpoints were also similar in the two groups. INTERPRETATION: In patients with an acute coronary syndrome, intravascular ultrasound-guided implantation of contemporary drug-eluting stents resulted in a lower 1-year rate of the composite outcome of cardiac death, target vessel myocardial infarction, or clinically driven revascularisation compared with angiography guidance alone. FUNDING: The Chinese Society of Cardiology, the National Natural Scientific Foundation of China, and Jiangsu Provincial & Nanjing Municipal Clinical Trial Project. TRANSLATION: For the Mandarin translation of the abstract see Supplementary Materials section.

Cardio protective effect of nicorandil in reperfusion injury among patients undergoing primary percutaneous coronary intervention.

Objectives: To evaluate the effect of nicorandil in prevention of reperfusion injury during primary percutaneous coronary intervention by thrombolysis in myocardial infarction flow grade scoring. Methods: A total of 140 patients from Rawalpindi Institute of Cardiology were enrolled in this study conducted from 7th September to 10th of October 2021. These participants were allocated into two major groups. Control group received conventional acute coronary syndrome protocol regimen only whereas experimental group was given nicorandil along with conventional acute coronary syndrome protocol. During primary percutaneous coronary intervention, thrombolysis in myocardial infarction flow grade scoring was analyzed and compared. Results: Majority of participants in nicorandil group achieved thrombolysis in myocardial infarction Grade-3 scoring which indicated reduced rate of no reflow phenomenon as compared to control group. A statistically significant difference was noted in score of both groups (p value = 0.001) signifying prophylactic use of nicorandil before primary percutaneous coronary intervention along with conventional acute coronary syndrome protocol is superior to only conventional acute coronary syndrome protocol regimen to cases in the control group. Conclusion: Use of nicorandil in ST elevated myocardial infarction patients before primary percutaneous coronary intervention prevents reperfusion injury thus decreasing the risk of post percutaneous coronary intervention complications and reducing mortality rate in cardiac patients suggesting its significant cardio protective role.

A case of aortic dissection in familial Mediterranean fever.

Familial Mediterranean fever (FMF) is an ethnicity-specific autoinflammatory disease prevalent in the Arab world. It has various presentations including amyloidosis, small-vessel vasculitis, and pericarditis. Different mutations in the Mediterranean fever (MEFV) gene can cause this disorder and it is inherited in an autosomal recessive pattern. We present a case of a 23-year-old man of Iranian descent with history of periodic fever, diagnosed as Stanford type A aortic dissection secondary to an acute attack of FMF. To the best of our knowledge, this is the first case reported of such a complication. .

Optical Coherence Tomography Guidance In The Management Of Acute Coronary Syndrome Based On Plaque Morphology.

BACKGROUND: Acute coronary syndrome (ACS) is one of the leading causes of death worldwide. It is characterized by the formation of coronary artery thrombus which can be either due to plaque rupture, plaque erosion or rupture of a calcific nodule. The aim of study was to assess the plaque morphology leading acute coronary syndrome using OCT and to guide management based on its findings. It was an observational study, conducted at Rawalpindi Institute of Cardiology from Jan to Dec 2019. METHODS: Fifty patients meeting the inclusion criteria were included in the study. OCT procedure was performed following intracoronary injection of 100-150 ug of nitroglycerine. The imaging catheter (OFDI dragon view) of the OCT device (Terumo Luna wave OFDI, Tokyo, Japan) was inserted into the culprit artery. Blood clearance was achieved by injecting diluted iodinated contrast at the rate of 5 ml/sec. Imaging acquisition was obtained following automated pullback at the rate of 25 mm/sec. Pathologies like stent under deployment, mal-apposition, strut fracture, plaque erosion, plaque rupture were assessed by the operating interventionist well versed with the OCT technology and lesion assessment. Data analysis was done using the SPSS version 26. Categorical variables were presented as counts and percentages while continuous variables as mean±SD. RESULTS: A total of 50 patients were included in the study. The mean age was 49.24±11.92. Majority of the patients were male comprising 78.0% of the cases. Plaque rupture was the most common underlying pathology seen in 32.5% of the patients and exclusively in STEMI patients which required stent deployment. Thin cap fibroatheroma was seen in 27.9% of the cases while lipid rich plaque in 23.2% of the cases; again, requiring stent deployment. 9.3% of the cases had plaque erosion while 4.6% had calcific nodule and only 2.3% had intramural hematoma which were treated conservatively. 42.8% of the stent thrombosis patients had under-deployed stents requiring balloon dilatation while 14.2% had mal-apposed stent again requiring balloon dilatation. In contrast 14.2% each had neo-atherosclerosis, stent strut fracture and uncovered stent struts as the underlying pathology for stent thrombosis each requiring stent deployment. CONCLUSIONS: OCT guided PCI in cases of acute coronary syndrome is a valuable modality that gives insight into the underlying pathology of the disease process and also guides in proper management.

A Case of Elephantiasis Nostras Verrucosa Secondary to Lymphedema Praecox Complicated by Congestive Cardiac Failure.

BACKGROUND In lymphedema, an imbalance in the formation and absorption of lymph causes accumulation of protein-rich fluid in the interstitium of the most gravity-dependent parts of the body. Diagnosis is usually made based on patient medical history and a physical examination showing a typical appearance of the affected body part. Differential diagnosis is confirmed by imaging. CASE REPORT Primary lymphedema is inherited in through an autosomal dominant pattern. Congestive cardiac failure and non-filarial infections predispose patients to the secondary form of lymphedema, elephantiasis nostras verrucosa (ENV). We present the case of a 65-year-old man with lymphedema praecox complicated by congestive cardiac failure. The patient was experiencing worsening left leg swelling and had a prior history of unilateral leg swelling at puberty. The condition was inherited through an autosomal dominant pattern, as his father, elder brother, and nephew were diagnosed with the same disease. The left leg showed non-pitting edema with indurated, woody skin and lichenification. The right leg had mild pitting edema. There were numerous verrucous folds and cobblestone-like nodules, and plaques and a painless ulcer on the left leg. Laboratory evaluation demonstrated an elevated B-type natriuretic peptide. He was treated with compression stockings and inelastic multi-layer bandaging and was administered limb decongestive treatment. After 1 week of therapy, his swelling had somewhat improved. CONCLUSIONS Various conditions can cause ENV and it can superimpose on any form of hereditary lymphedema. The most effective strategy for this condition seems to be a thorough workup of the underlying cause of the ENV and early intervention.

Optical coherence tomography: assessment of coronary artery disease and guide to percutaneous coronary intervention.

BACKGROUND AND AIMS: Angiographic guidance for percutaneous coronary intervention (PCI) has significant limitations in interpretation. The superior spatial resolution of optical coherence tomography (OCT) can provide meaningful clinical benefits, although limited data is available on Asian populations. This study aimed to determine whether OCT can provide additional advantages and useful clinical information beyond that obtained by angiography alone in decision making for PCI. METHODS: This was an observational study based on a single tertiary cardiac center in Pakistan, which includes 67 patients who underwent coronary angiogram and stenting. Their pre and post stenting OCT findings were recorded. Any additional intervention was also recorded. The data were analysed using IBM SPSS software version 26.0. RESULTS: The mean age was 55.00 ± 9.00 years. Majority of the patients were males (65.7%). On angiography, there was an equal number of stable and ruptured plaques (38.8%). Post stenting results showed 29.9% under deployed stents and 34.3% were either undersized or mal-apposed. Out of 67 patients, 50 (74.6%) needed re-intervention after PCI. Among different procedures, post-dilatation was most common. CONCLUSION: The main OCT benefit is in borderline lesions on CA, in whom OCT identifies significant coronary stenosis and leads to PCI indication in patients. In the post-PCI context, OCT leads to an indication of PCI optimisation in half of the coronary lesions.

Subclinical Left Ventricular Dysfunction In Patients With Isolated Severe Rheumatic Mitral Stenosis Having Normal Left Ventricular Ejection Fraction.

BACKGROUND: Mitral stenosis (MS) is a prevalent disease in the developing world. It is a preventable disease associated with considerably high morbidity and mortality rates. Myocarditis secondary to rheumatic MS can cause left ventricular (LV) dysfunction. In majority of the case this LV dysfunction is subclinical. Recent development in imaging techniques like tissue Doppler imaging (TDI) and strain imaging enabled us to detect subclinical LV dysfunction. One such example is Global Longitudinal Strain (GLS), which is a reliable mean of assessing LV dysfunction in patients diagnosed with mitral stenosis. This study is design to determine the frequency of subclinical LV dysfunction in patients presenting with severe MS of rheumatic etiology in our institute. Objective of the study was to determine frequency of subclinical LV dysfunction by mean GLS in patients with isolated severe Rheumatic MS having normal LV Ejection fraction measured by 2D/M-mode echocardiography. It was an observational crosssectional study, conducted at Department of Cardiology, Rawalpindi Institute of Cardiology, Rawalpindi, during the period of six months from 1st January to 30th June 2016. METHODS: Fiftyfive patients with isolated severe mitral stenosis of underlying rheumatic aetiology with preserve LV function (EF>50%) were selected as per other inclusion and exclusion criteria. All patients were evaluated with detailed history, physical examination and echocardiographic examination. GLS was also noted and all other information was recorded on data collection form. RESULTS: The average age and mean GLS was 48.20±11.62 years and -19.24±1.15% respectively. Left ventricular systolic impairment in patients under study using the Global Longitudinal Strain was seen in 16.36% (9/55) cases. CONCLUSIONS: Our results suggest that GLS helps in detecting impairment of LV systolic function at an early stage in patients with mitral stenosis which helps in their risk stratification thus warranting their early management.

A Single Coronary Artery with an Absent Right Coronary and a Superdominant Left Circumflex Giving off a Branch Supplying the Right Coronary Artery Territory.

An absent right coronary artery (RCA) with single left coronary artery (LCA) originating from left aortic sinus with a superdominant left circumflex (LCX) and giving off an RCA branch is one of the rarest coronary artery anomalies. It occurs with an incidence of less than 0.1%. Usually, patients are asymptomatic and abnormality is found incidentally on cardiac catheterisation or CT angiography. We present a case report of an unusual coronary anomaly in a patient who presented with anterior myocardial infarction. Patient was subjected to coronary angiography, which revealed absent RCA originating from distal LCX artery, supplying the base of heart and RCA territory. He underwent primary percutaneous intervention (PCI) with stenting to the left anterior descending (LAD) artery. This type of anomaly, in which single LCA from which dominant LCX continues as RCA, is important to diagnose and manage if diseased, as stenosis of the dominant LCX artery in such cases can jeopardise a large portion of myocardium, which can lead to increased morbidity and mortality, if left untreated.

Acute Pulmonary Embolism: Presentation, Diagnosis, Management and Factors Impacting Clinical Outcome in a Tertiary Cardiac Centre in Pakistan.

OBJECTIVE: To evaluate the presentation, diagnosis, management and outcome of acute pulmonary embolism for assessing the factors impacting mortality in such patients. STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: Rawalpindi Institute of Cardiology, Rawalpindi, Pakistan, from July 2015 to July 2018. METHODOLOGY: Patients presenting with clinical suspicion of pulmonary embolism were subjected to a diagnostic algorithm consisting of Wells Rule, D-Dimer testing, echocardiography and CT pulmonary angiogram. Patients diagnosed with pulmonary embolism were subdivided into massive and submassive pulmonary embolism groups. Most patients diagnosed with massive pulmonary embolism were treated with streptokinase injection. For those diagnosed as submassive pulmonary embolism, the standard therapy remained anticoagulation with intravenous heparin, both the subsets of patients were further put on oral warfarin. Clinical outcome was defined as combined end-point including death during hospital stay, recurrence of PE and meed for repeat thrombolysis. RESULTS: A total of 174 patients diagnosed with pulmonary embolism were studied. The mean age was 49.1 +14.8 years (range 23-88 years) with 109 (62.6%) patients being male. The in-hospital clinical course was uneventful in 144 (83%) patients. Twenty-two patients (12.6%) patients died, of whom 3 died from major bleeding, one from cancer, and 18 from the pulmonary embolism process (14 patients from refractory shock and 4 patients from recurrent PE). A total of 8 (4.6%) had fatal or non-fatal recurrent PE. In patients who had echocardiography both pre- and post-thrombolysis, initial RV dysfunction was reversible in 136 (78%) within 48h following thrombolytic therapy. By univariate analysis, only shock (SBP) and delay in diagnosis for more than 6 hours were associated with adverse event. CONCLUSION: Early diagnosis by doing urgent CTPA in patients with suspected acute PE is the cornerstone in reducing mortality in acute PE patients.

Optical Coherence Tomography-guided Intervention in STEMI Patients with Normal Looking Coronaries.

Optical coherence tomography (OCT) is an increasingly available intracoronary imaging modality that provides highresolution imaging of coronary arteries and guides operators in percutaneous coronary intervention (PCI) by accurately defining luminal geometry and detailed plaque composition. The two cases under discussion in this report, presented with acute ST elevation myocardial infarction (STEMI) with angiography showing minor narrowing (<30%) with TIMI III flow in which OCT-guided approach was used regarding the management owing to its improved temporal and axial resolution, thus providing proper plaque assessment and subsequent proper management.

Assessment of Predictors of Side Branch Occlusion after Main Vessel Stenting in Coronary Bifurcation Lesions in Patients Undergoing Percutaneous Coronary Intervention.

OBJECTIVE: To determine the frequency of side branch (SB) occlusion during percutaneous coronary intervention (PCI) with stenting of bifurcation lesions and to assess the predictors of side branch occlusion in local population. STUDY DESIGN: Cross-sectional study. PLACE AND DURATION OF STUDY: Cardiac Catheterization Lab, Rawalpindi Institute of Cardiology, Rawalpindi, from July 2016 to January 2017. METHODOLOGY: A total of 200 patients fulfilling the inclusion criteria were included in the study with non-probability consecutive sampling technique. Variables like diameters and lesion lengths of main vessel and side branch were recorded using quantitative coronary analysis software (QCA). The SB occlusion was defined as <3 TIMI score following main vessel PCI with stenting. The data was analysed using SPSS version 21.0. RESULTS: Mean age (years) of the study population was 52.27 ±13.33 including 180 (90.0%) male and 20 (10.0%) female patients. SB occlusion was observed in 15 (7.5%) of cases. Mean SB diameter was significantly larger in cases without SB occlusion than those with SB occlusion (2.06 ±0.09 vs. 2.17 ±0.26, p=0.003). Similarly, SB lesions were significantly shorter in length in those without SB occlusion than those with SB occlusion (3.53 ±0.51 and 4.66 ±3.11, p<0.001). However, mean MV diameter (mm) and mean MV lesions length (mm) in both the groups were statistically not significant. CONCLUSION: Mean SB diameter and lesion length are useful predictors of SB occlusion during stenting of bifurcation lesions in the local population.

Hyperdominant Left Anterior Descending Artery: ARare Coronary Artery Anomaly.

The posterior descending artery supplying the posterior one-third of the inter ventricular septum usually arise from the right coronary artery (RCA) or the left circumflex artery (LCx). Posterior descending artery arising from the left anterior descending artery is a rare anomaly. A66-year man presented with chest pain, ECG changes, and raised biomarkers. A diagnosis of non-STelevation myocardial infarction was made. Coronary angiogram, done on the next day, revealed the posterior descending artery as a continuation of the left anterior descending artery (LAD) beyond the crux and a rudimentary right coronary artery. The left anterior descending artery had subcritical stenosis in proximal course (confirmed on fractional flow reserve) and was advised medical treatment.

Validity of Electrocardiographic QT Interval in Predicting Left Ventricular Diastolic Dysfunction in Patients with Suspected Heart Failure.

OBJECTIVE: To determine the validity of electrocardiographic QT interval in predicting left ventricular diastolic dysfunction in patients with suspected heart failure using echocardiogram as the gold standard. STUDY DESIGN: Cross-sectional validation study. PLACE AND DURATION OF STUDY: AFIC-NIHD, Rawalpindi, from December 2012 to June 2013. METHODOLOGY: Patients with suspected heart failure undergoing 12-lead electrocardiogram and echocardiography were inducted. All electrocardiograms were analyzed by a single trained reader unaware of the echocardiographic findings. QTc interval was calculated according to the published guidelines. All patients underwent a complete M mode, 2 dimensional, Doppler, and tissue Doppler echocardiography using aiE33 ultrasound system and diastolic dysfunction was calculated. RESULTS: Three hundred patients were studied. Descriptive statistics of age was 61.42 years ±10.43. Of all the patients 218 patients (72.7%) were male and 82 patients were female (27.3%). Mean QT interval (msec) was 427.29 ±54.69. One hundred and eighty patients (60.0%) had diastolic dysfunction and 120 patients (40%) had no diastolic dysfunction. The sensitivity of electrocardiographic QTc interval in predicting diastolic dysfunction was 71.11% and specificity was 88.11%. CONCLUSION: Prolonged electrocardiographic QTc interval in patients with suspected heart failure is a useful tool in predicting diastolic dysfunction.

Percutaneous Coronary Intervention Under Cover of Left Ventricular Assist Device (Impella 2.5).

Impella 2.5 is a temporary left ventricular assist device that is being increasingly used in high risk Percutaneous Coronary intervention (PCI). It reduces the cardiac workload and provides assistance to myocardium and vital organs in states of severe left ventricular dysfunction and cardiogenic shock. We report the first case of successful percutaneous coronary stenting performed in a high risk patient using impella 2.5. A 65-year old diabetic and hypertensive male with a known double vessel coronary artery disease and a reduced left ventricular function (ejection fraction, 20%) was admitted with intractable angina. He was on optimal medical treatment for 2 months. His coronary angiogram done 2 months back had revealed double vessel coronary artery disease (subtotally occluded co-dominant left circumflex and moderate 60% stenosis in left anterior descending artery and a normal co-dominant right coronary artery). He was considered a high risk both for Coronary Artery Bypass Graft (CABG) surgery and PCI due to co-morbidities and reduced left ventricular function. As he had failed a trial of optimal medical therapy and the cardiac surgeon's reluctance for surgery, the patient and his family was counseled for high risk PCI with left ventricular assist device using the impella 2.5.