Multi-Center Experience of Coronary Artery Perforation During Percutaneous Coronary Intervention: Clinical and Angiographic Characteristics, Management, and Outcomes Between 2010 and 2020.

BACKGROUND: Coronary artery perforations are one of the most feared, rare, and catastrophic complication of percutaneous coronary intervention. Despite the remarkable increase in coronary angiography and percutaneous coronary intervention, there is no large database that collects coronary artery perforation for the Turkish population. Our study aimed to report our experience over a 10-year period for clinical and angiographic characteristics, management strategies, and outcomes of coronary artery perforation during the percutaneous coronary intervention at different cardiology departments in Turkey. METHODS: The study data came from a retrospective analysis of 48 360 percutaneous coronary intervention procedures between January 2010 and June 2020. A total of 110 cases who had coronary artery perforation during the percutaneous coronary intervention were found by angiographic review. Analysis has been performed for the basic clinical, angiographic, procedural characteristics, the management of coronary artery perforation, and outcome of all patients. RESULTS: The coronary artery perforation rate was 0.22%. Out of 110 patients with coronary artery perforation, 66 patients showed indications for percutaneous coronary intervention with acute coronary syndrome and 44 patients with stable angina pectoris. The most common lesion type and perforated artery were type C (34.5%) and left anterior descending (41.8%), respectively. The most observed coronary artery perforation according to Ellis classification was type III (37.2%). Almost 52.7% of patients have a covered stent implanted in the perforated artery. The all-cause mortality rate of coronary artery perforation patients in the hospital was 18.1%. CONCLUSION: The observed rate of coronary artery perforation in our study is consistent with the studies in this literature. However, the mortality rates related to coronary artery perforation are higher than in other studies in this literature. Especially, the in-hospital mortality rate was higher in type II and type III groups due to perforation and its complications. Nevertheless, percutaneous coronary intervention should be done in selected patients despite catastrophic complications.

HbA1c, Coronary atheroma progression and cardiovascular outcomes.

BACKGROUND AND AIMS: We tested the hypothesis that on-treatment HbA1c levels independently associate with coronary atheroma progression and major adverse cardiovascular events (MACE: death, myocardial infarction, cerebrovascular accident, coronary revascularization, or hospitalization for unstable angina) rates. METHODS: We performed a post-hoc pooled analysis of data from seven prospective, randomized trials involving serial coronary intravascular ultrasonography (IVUS). The percent atheroma volume (PAV) was calculated as the proportion of the entire vessel wall occupied by atherosclerotic plaque. Using multivariable mixed modeling, we determined the association of on-treatment HbA1c with annualized change in PAV. Cox proportional hazard models were used to assess the association of HbA1c with incidence of MACE. RESULTS: Among 3,312 patients (mean age 58.6±9years, 28.4%women) average on-treatment HbA1c was 6.2±1.1%. Overall, there was no net significant annualized change in PAV (0.12±0.19%, p = 0.52). In a fully adjusted multivariable analysis (following adjustment of age, sex, body mass index, systolic blood pressure, smoking, low- and high-density lipoprotein cholesterol, triglyceride levels, peripheral vascular disease, trial, region, and baseline PAV), higher on-treatment HbA1c levels were independently associated with annualized changes in PAV [beta-estimate (95% confidence interval): 0.13(0.08, 0.19), p < 0.001]. On-treatment HbA1c levels were independently associated with MACE [hazard ratio (95% confidence interval): 1.13(1.04, 1.23), p = 0.005]. CONCLUSIONS: Independent of achieved cardiovascular risk factor control, greater HbA1c levels significantly associate with coronary atheroma progression rates and clinical outcomes. These results support the notion of a direct, specific effect of glycemic control upon coronary atheroma and atherosclerotic events, supporting the rationale of therapies designed to directly modulate it.

Type 1 Kounis Syndrome Induced by Inactivated SARS-COV-2 Vaccine.

Background Vaccination is the most important way out of the novel coronavirus disease 2019 (COVID-19) pandemic. Vaccination practices have started in different countries for community immunity. In this process, health authorities in different countries have preferred different type of COVID-19 vaccines. Inactivated COVID-19 vaccine is one of these options and has been administered to more than 7 million people in Turkey. Inactivated vaccines are generally considered safe. Kounis syndrome (KS) is a rare clinical condition defined as the co-existence of acute coronary syndromes and allergic reactions. Case Report We present the case of a 41-year-old woman with no cardiovascular risk factors who was admitted at our emergency department with flushing, palpitation, dyspnea, and chest pain 15 min after the first dose of inactivated CoronaVac (Sinovac Life Sciences, Beijing, China). Electrocardiogram (ECG) showed V4-6 T wave inversion, and echocardiography revealed left ventricular wall motion abnormalities. Troponin-I level on arrival was elevated. Coronary angiography showed no sign of coronary atherosclerosis. She was diagnosed with type 1 KS. The patient's symptoms resolved and she was discharged from hospital in a good condition. Why Should an Emergency Physician Be Aware of This? To the best of our knowledge, this is the first case of allergic myocardial infarction secondary to inactivated coronavirus vaccine. This case demonstrates that KS can occur after inactivated virus vaccine against COVID-19. Although the risk of severe allergic reaction after administration of CoronaVac seems to be very low, people who developed chest pain after vaccine administration should be followed by ECG and troponin measurements.

CHA2DS2-VASc score and modified CHA2DS2-VASc score can predict mortality and intensive care unit hospitalization in COVID-19 patients.

In this study, we investigated whether the CHA2DS2-VASc score could be used to estimate the need for hospitalization in the intensive care unit (ICU), the length of stay in the ICU, and mortality in patients with COVID-19. Patients admitted to Merkezefendi State Hospital because of COVID-19 diagnosis confirmed by RNA detection of virus by using polymerase chain reaction between March 24, 2020 and July 6, 2020, were screened retrospectively. The CHA2DS2-VASc and modified CHA2DS2-VASc score of all patients was calculated. Also, we received all patients' complete biochemical markers including D-dimer, Troponin I, and c-reactive protein on admission. We enrolled 1000 patients; 791 were admitted to the general medical service and 209 to the ICU; 82 of these 209 patients died. The ROC curves of the CHA2DS2-VASc and M-CHA2DS2-VASc scores were analyzed. The cut-off values of these scores for predicting mortality were ≥ 3 (2 or under and 3). The CHA2DS2-VASc and M-CHA2DS2-VASc scores had an area under the curve value of 0.89 on the ROC. The sensitivity and specificity of the CHA2DS2-VASc scores were 81.7% and 83.8%, respectively; the sensitivity and specificity of the M-CHA2DS2-VASc scores were 85.3% and 84.1%, respectively. Multivariate logistic regression analysis showed that CHA2DS2-VASc, Troponin I, D-Dimer, and CRP were independent predictors of mortality in COVID-19 patients. Using a simple and easily available scoring system, CHA2DS2-VASc and M-CHA2DS2-VASc scores can be assessed in patients diagnosed with COVID-19. These scores can predict mortality and the need for ICU hospitalization in these patients.

Warfarin Use Is Associated With Progressive Coronary Arterial Calcification: Insights From Serial Intravascular Ultrasound.

OBJECTIVES: This study compared serial changes in coronary percent atheroma volume (PAV) and calcium index (CaI) in patients with coronary artery disease who were treated with and without warfarin. BACKGROUND: Warfarin blocks the synthesis and activity of matrix Gla protein, a vitamin K-dependent inhibitor of arterial calcification. The longitudinal impact of warfarin on serial coronary artery calcification in vivo in humans is unknown. METHODS: In a post hoc patient-level analysis of 8 prospective randomized trials using serial coronary intravascular ultrasound examinations, this study compared changes in PAV and CaI in matched arterial segments in patients with coronary artery disease who were treated with (n = 171) and without (n = 4,129) warfarin during an 18- to 24-month period. RESULTS: Patients (mean age 57.9 ± 9.2 years; male 73%; prior and concomitant 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statin) use, 73% and 97%, respectively) demonstrated overall increases in PAV of 0.41 ± 0.07% (p = 0.001 compared with baseline) and in CaI (median) of 0.04 (interquartile range [IQR]: 0.00 to 0.11; p < 0.001 compared with baseline). Following propensity-weighted adjustment for clinical trial and a range of clinical, ultrasonic, and laboratory parameters, there was no significant difference in the annualized change in PAV in the presence and absence of warfarin treatment (0.33 ± 0.05% vs. 0.25 ± 0.05%; p = 0.17). A significantly greater annualized increase in CaI was observed in warfarin-treated compared with non-warfarin-treated patients (median 0.03; IQR: 0.0 to 0.08 vs. median 0.02; IQR: 0.0 to 0.06; p < 0.001). In a sensitivity analysis evaluating a 1:1 matched cohort (n = 164 per group), significantly greater annualized changes in CaI were also observed in warfarin-treated compared with non-warfarin-treated patients. In a multivariate model, warfarin was independently associated with an increasing CaI (odds ratio: 1.16; 95% confidence interval: 1.05 to 1.28; p = 0.003). CONCLUSIONS: Warfarin therapy is associated with progressive coronary atheroma calcification independent of changes in atheroma volume. The impact of these changes on plaque stability and cardiovascular outcomes requires further investigation.

Atrial fibrillation, progression of coronary atherosclerosis and myocardial infarction.

Background Despite atrial fibrillation representing an established risk factor for stroke, the association between atrial fibrillation and both progression of coronary atherosclerosis and major adverse cardiovascular events is not well characterized. We assessed the serial measures of coronary atheroma burden and cardiovascular outcomes in patients with and without atrial fibrillation. Methods Data were analyzed from nine clinical trials involving 4966 patients with coronary artery disease undergoing serial intravascular ultrasonography at 18-24 month intervals to assess changes in percent atheroma volume (PAV). Using a propensity weighted analysis, and following adjustment for baseline variables, patients with ( n = 190) or without ( n = 4776) atrial fibrillation were compared with regard to coronary plaque volume and major adverse cardiovascular events (death, myocardial infarction, and stroke). Results Atrial fibrillation patients demonstrated lower baseline PAV (36.0 ± 8.9 vs. 38.1 ± 8.9%, p = 0.002) and less PAV progression (-0.07 ± 0.34 vs. + 0.23 ± 0.34%, p = 0.001) compared with the non-atrial fibrillation group. Multivariable analysis revealed atrial fibrillation to independently predict both myocardial infarction [HR, 2.41 (1.74,3.35), p<0.001] 2.41 (1.74, 3.35), p < 0.00) and major adverse cardiovascular events [HR, 2.2, (1.66, 2.92), p<0.001] 2.20 (1.66, 2.92), p < 0.001]. Kaplan-Meier analysis showed that atrial fibrillation compared with non-atrial fibrillation patients had a significantly higher two-year cumulative incidence of overall major adverse cardiovascular events (4.4 vs. 2.0%, log-rank p = 0.02) and myocardial infarction (3.3 vs. 1.5%, log-rank p = 0.05). Conclusions The presence of atrial fibrillation independently associates with a heightened risk of myocardial infarction despite a lower baseline burden and progression rate of coronary atheroma. Further studies are necessary to define the pathogenesis of myocardial infarction in the setting of atrial fibrillation.

A novel association between TGFb1 and ADAMTS4 in coronary artery disease: A new potential mechanism in the progression of atherosclerosis and diabetes.

OBJECTIVE: Coronary artery disease is characterized by atherosclerosis in the vessel wall. Recently, it has been thought that increasing LDL-binding capacity of subendothelial proteoglycan fragments that are formed by protease activity can be responsible for the initiation of atherosclerosis. ADAMTS4 is a member of the versican-degrading proteinases. In vitro studies demonstrated that TGFb inhibits the expression of ADAMTS4 in macrophages. In this study, we aimed to investigate the role and association between TGFb1 and ADAMTS4 in coronary artery disease. METHODS: A total of 84 cases with atheroma plaque and 72 controls without plaque were analyzed. The severity of disease was determined by Gensini score. TGFb1 gene polymorphisms were genotyped by the PCR-RFLP method. TGFb1 and ADAMTS4 serum levels were measured by ELISA method. Statistical analyses of genotypes and their relationship with serum levels were performed by chi-square, student t test and ANOVA. RESULTS: ADAMTS4 levels were higher in cases compared with controls (p<0.05). In the patient group, ADAMTS4 levels were higher than in controls and correlated with TGFb1 serum levels (r=0.29; p<0.05) and severity of disease (r=0.20; p<0.05). The TGFb1 gene CCA haplotype was associated with 3.3-fold increase in coronary artery disease (OR=3.26 95% CI 1.22-8.68; p<0.05). Unexpectedly, ADAMTS4 serum levels were also higher in diabetic cases (p=0.05). CONCLUSION: This study has demonstrated that ADAMTS4 may be responsible for the pathogenesis of atherosclerosis. This is the first report about the association between ADAMTS4 and TGFb1 serum levels in the progression of atherosclerosis in CAD. Furthermore, it is seen that TGFb1 haplotype can cause a genetic susceptibility to CAD in the Turkish population. To our knowledge, this is also the first report suggesting higher serum ADAMTS4 levels in diabetic patients.

Evaluation of the prevalence of coronary artery disease in patients with valvular heart disease.

OBJECTIVES: The aim of the present study was to retrospectively evaluate the prevalence of concurrent coronary artery disease in patients who underwent surgery due to severe valvular heart disease. The study also investigated the association of coronary artery disease with the type of valvular heart disease. MATERIALS AND METHODS: A total of 241 patients (123 females [51%]), who had underwent single valvular heart surgery, were included in the study. The patients who underwent valve replacement surgery were divided into four groups: patients with severe mitral stenosis (MS), patients with severe mitral regurgitation (MR), patients with severe aortic regurgitation (AR), and patients with severe aortic stenosis (AS). Age, DM, HT, history of smoking, and LDL values were recorded as the risk factors for CAD. RESULTS: Coronary artery disease was detected in 26.4% of patients with mitral stenosis and 57.7% of patients with aortic stenosis. Of the patients with mitral insufficiency, 41.9% had CAD, and 44.4% of the patients with aortic insufficiency had CAD. CONCLUSION: The comparison of MS and AS groups revealed significantly higher prevalence of CAD in the AS group. There was no statistically significant difference between the MR and AR groups in terms of the prevalence of CAD. The comparison of MS and MR groups revealed significantly higher prevalence of CAD in the MR group. Furthermore, the comparison of these groups in terms of the extensiveness of the coronary artery disease revealed significantly higher Gensini score in the MR group.

Sudden death of a pregnant woman in third trimester with no risk factor.

Acute myocardial infarction in pregnancy is rare and life-threatening for both the mother and the fetus. We present the case of a 31-year-old previously healthy woman with no risk factors at 32 weeks of gestation who applied with vomiting, dyspnea and orthopnea. A respiratory arrest developed followed by loss of the fetal viability, cardiac arrest, and failure of resuscitation. We aim to raise awareness about the clinical approach to pregnant patients who are to be considered with a broad spectrum of differential diagnosis.

Serum and pleural fluid N-Terminal-Pro-B-Type natriuretic peptide concentrations in the differential diagnosis of pleural effusions.

Currently, new biomarkers like N-Terminal-Pro-B-Type natriuretic peptide (NT-proBNP) have been used in the differential diagnosis of pleural effusions. In our study, we aimed to investigate the diagnostic value of NT-proBNP, especially in cardiac originated pleural effusions. Forty-five patients with pleural effusions were included in the study. NT-proBNP levels and biochemical markers involved in the Light's criteria were analyzed in pleural fluid and serums of the patients. Pleural fluid culture, AFB smear, cytology were performed where they were indicated according to the clinical evaluation. In patients, to whom cardiac pathology was considered to be; cardiological evaluation and echocardiography were also done. Thirty-eight pleural effusions were exudative and, 7 were transudative according to the Light's criteria. Final diagnosis were malignant effusion in 13, infection (tuberculosis/pneumonia) in 10, congestive heart failure in 21, and other conditions related with pleural effusion in 1 of the patients. Median (25th to 75th percentiles) NT-proBNP levels of serum and pleural fluid due to congestive heart failure (CHF) were 4747 pg/mL (931-15754) and 4827 pg/mL (1290-12.430) while median NT-proBNP levels of serum and pleural fluid related with non-cardiac reasons were 183 pg/mL (138-444) and 245 pg/mL (187-556) respectively. NT-proBNP levels of serum and pleural fluid were significantly high in CHF (p< 0.001 for both). When four groups were compared serum and pleural fluid NT-proBNP levels were highest in the CHF group which was followed by malignancy, infection and others (p< 0.001 for both). Fourteen of 21 patients who were accepted to have congestive heart failure as the final diagnosis by a cardiological evaluation had an exudative pleural fluid according to the Light's criteria. Serum and pleural fluid NT-proBNP levels were higher in transudates and this reached statistically significance for pleural fluid (p= 0.009). We suggest that measurement of pleural fluid NT-proBNP is a smart approach and pleural fluid NT-proBNP can reflect cardiac origin of effusions better than serum NT-proBNP and Light's criteria.

[Beyond lowering LDL cholesterol]. / LDL kolesterolü düsürmenin ötesi.

Compelling evidence from randomized controlled studies demonstrated the crucial role of lowering low-density lipoprotein cholesterol (LDL-C) in the prevention of vascular events. However, not all patients with low LDL-C levels show similar reduction in event rates. The residual risk factors associated with ongoing vascular events despite achieving low LDL-C levels remain to be elucidated. New data suggest that beyond statin therapy, inflammatory mediators, high non-HDL (high-density lipoprotein) cholesterol or apolipoprotein B, small dense LDL-C, type 2 diabetes mellitus, and lifestyle features may have impact on residual vascular risk. In this review, we discussed the significance of identifying these residual risk factors and developing new treatment strategies to further decrease vascular events. The importance of imaging arterial wall to evaluate the effect of various medical therapies has also stated.

Lowering the triglyceride/high-density lipoprotein cholesterol ratio is associated with the beneficial impact of pioglitazone on progression of coronary atherosclerosis in diabetic patients: insights from the PERISCOPE (Pioglitazone Effect on Regression of Intravascular Sonographic Coronary Obstruction Prospective Evaluation) study.

OBJECTIVES: The purpose of this study was to determine the factors associated with the favorable effect of pioglitazone on atheroma progression. BACKGROUND: Diabetes mellitus is associated with accelerated coronary atheroma progression. Pioglitazone slowed progression compared with glimepiride in this population. METHODS: In all, 360 diabetic patients with coronary artery disease were treated with pioglitazone or glimepiride for 18 months in the PERISCOPE (Pioglitazone Effect on Regression of Intravascular Sonographic Coronary Obstruction Prospective Evaluation) study. Coronary atheroma progression was evaluated by serial intravascular ultrasound. The relationship between changes in biochemical parameters, percent atheroma volume, and total atheroma volume was investigated. RESULTS: Pioglitazone-treated patients demonstrated greater increases in high-density lipoprotein cholesterol (HDL-C) and reductions in glycated hemoglobin, triglycerides, and C-reactive protein. Significant correlations were observed between changes in percent atheroma volume and triglycerides (r = 0.15, p = 0.04), triglyceride/HDL-C ratio (r = 0.16, p = 0.03), and glycated hemoglobin (r = 0.16, p = 0.03) with pioglitazone, and changes in low-density lipoprotein cholesterol (r = -0.15, p = 0.05), apolipoprotein B (r = -0.16, p = 0.04), and apolipoprotein A-I (r = -0.20, p = 0.01) with glimepiride. Substantial atheroma regression, compared to progression, was associated with greater relative increases in HDL-C (14.2% vs. 7.8%, p = 0.04), relative decreases in triglycerides (-13.3% vs. -1.9%, p = 0.045), triglyceride/HDL-C ratio (-22.5 vs. -9.9%, p = 0.05), and decrease in glycated hemoglobin (-0.6% vs. -0.3%, p = 0.01). Multivariable analysis revealed that pioglitazone-induced effects on triglyceride/HDL-C were associated with changes in percent atheroma volume (p = 0.03) and total atheroma volume (p = 0.02). CONCLUSIONS: Favorable effects of pioglitazone on the triglyceride/HDL-C ratio correlated with delayed atheroma progression in diabetic patients. This finding highlights the potential importance of targeting atherogenic dyslipidemia in diabetic patients with coronary artery disease.

Plaque progression in coronary arteries with minimal luminal obstruction in intravascular ultrasound atherosclerosis trials.

The relation among the burden of disease, progression of atherosclerosis, and remodeling in angiographically minimally diseased coronary arteries has not been defined. The present analysis included 1,906 patients who participated in 5 prospective clinical trials examining atheroma progression using intravascular ultrasonography. For the present analysis, the patients were stratified according to baseline quantitative coronary angiographic stenosis: <20%, 20% to 35%, and >35%. Patients with a lesser degree of luminal stenosis had less atherosclerosis. However, in the arteries with minimal angiographic stenosis, a large percentage of images contained atheroma, demonstrating the diffuse nature of coronary atherosclerosis. All 3 groups showed evidence of disease progression. The serial changes in vessel dimensions revealed that both the external elastic membrane and lumen volumes decreased in all 3 subgroups, in keeping with vessel and luminal constriction. In conclusion, these findings have demonstrated that patients with at least one luminal stenosis have diffuse atherosclerosis that progressed during 18 to 24 months, making them a target for therapeutic intervention. These minimally diseased arteries demonstrated evidence of vessel and luminal constriction, regardless of the angiographic appearance.

Comparison of rates of progression of coronary atherosclerosis in patients with diabetes mellitus versus those with the metabolic syndrome.

Diabetes mellitus (DM) and metabolic syndrome (MS) are associated with adverse cardiovascular outcomes. However, the extent and progression of coronary atherosclerosis for these conditions have not been directly compared. Three thousand four hundred fifty-nine patients with coronary artery disease underwent serial evaluation of atheroma burden by intravascular ultrasound. Patients with DM, MS, or neither diagnosis were compared with regard to plaque burden, progression, and arterial remodeling. Among the 3 groups, patients with MS had the largest number of individual cardiovascular risk factors. Patients with DM demonstrated more extensive atherosclerosis burden with a greater percent atheroma volume compared to patients with MS or those with neither diagnosis (40.3 +/- 9.0%, 37.6 +/- 8.9%, and 38.1 +/- 9.1%, p <0.001) and total atheroma volume (198.3 +/- 85.9, 190.7 +/- 85.0, and 186.3 +/- 79.1 mm(3), p = 0.05). MS compared to neither diagnosis was accompanied by expansion of the external elastic membrane (501.3 +/- 174.3 vs 484.4 +/- 160.7 mm(3), p = 0.02), whereas DM was associated with lumen constriction (290.6 +/- 111.7 vs 298.1 +/- 105.5 mm(3), p <0.0001). On serial evaluation, DM, but not MS, was associated with greater progression of percent atheroma volume compared to neither diagnosis (+0.8 +/- 0.3, +0.3 +/- 0.2, and +0.1 +/- 0.2%, p <0.0001) and total atheroma volume (-1.0 +/- 1.8, -3.3 +/- 1.8, and -4.0 +/- 1.8 mm(3), p = 0.001). Meeting criteria for MS was not associated with greater disease progression in patients with DM. In conclusion, despite having fewer individual risk factors, DM is associated with greater plaque progression and more constrictive remodeling than MS. This finding highlights the deleterious effects of DM on the arterial wall independent of its associated metabolic abnormalities.

Clinical predictors of plaque progression despite very low levels of low-density lipoprotein cholesterol.

OBJECTIVES: The purpose of this study was to characterize the determinants of plaque progression despite achieving very low levels of low-density lipoprotein cholesterol (LDL-C). BACKGROUND: Despite achieving very low levels of LDL-C, many patients continue to demonstrate disease progression and have clinical events. METHODS: A total of 3,437 patients with coronary artery disease underwent serial intravascular ultrasound examination in 7 clinical trials. Patients who achieved an on-treatment LDL-C level of 20% of patients continued to progress. There were no demographic differences between groups. Progressors demonstrated higher baseline levels of glucose (117.1 +/- 42.5 mg/dl vs. 112.1 +/- 40.0 mg/dl, p = 0.02), triglycerides (157.5 mg/dl vs. 133.0 mg/dl, p = 0.004), and a smaller decrease of apolipoprotein B (-25.1 +/- 3.4 mg/dl vs. -27.4 +/- 3.35 mg/dl, p = 0.01) at follow-up. Multivariable analysis revealed that independently associated risk factors of progression in patients with LDL-C

Intravascular ultrasound-derived measures of coronary atherosclerotic plaque burden and clinical outcome.

OBJECTIVES: The aim of this study was to investigate the relationship between intravascular ultrasound (IVUS)-derived measures of atherosclerosis and cardiovascular outcomes. BACKGROUND: IVUS has been used in clinical trials to evaluate the effect of medical therapies on coronary atheroma progression. METHODS: Coronary plaque progression was evaluated in 4,137 patients in 6 clinical trials that used serial IVUS. The relationship between baseline and change in percent atheroma volume (PAV) and total atheroma volume with incident major adverse cardiovascular events (MACE) was investigated. RESULTS: PAV increased by 0.3% (p < 0.001), and 19.9% of subjects experienced MACE (0.9% death, 1.8% myocardial infarction, 18.9% coronary revascularization). Greater baseline PAVs were observed in patients who experienced myocardial infarctions (42.2 +/- 9.6% vs. 38.6 +/- 9.1%, p = 0.001), coronary revascularization (41.2 +/- 9.3% vs. 38.1 +/- 9.0%, p < 0.001), or MACE (41.3 +/- 9.2% vs. 38.0 +/- 9.0%, p < 0.001). Each standard deviation increase in PAV was associated with a 1.32-fold (95% confidence interval: 1.22 to 1.42; p < 0.001) greater likelihood of experiencing a MACE. During follow-up (21.1 +/- 3.7 months), greater increases in PAV, but not total atheroma volume, were observed in subjects who experienced MACE compared with those who did not (0.95 +/- 0.19% vs. 0.46 +/- 0.16%, p < 0.001). Each standard deviation increase in PAV was associated with a 1.20-fold (95% confidence interval: 1.10 to 1.31; p < 0.001) greater risk for MACE. Multivariate analysis revealed that factors associated with MACE included baseline PAV (p < 0.0001), change in PAV (p = 0.002), smoking (p = 0.0002) and hypertension (p = 0.01). CONCLUSIONS: A direct relationship was observed between the burden of coronary atherosclerosis, its progression, and adverse cardiovascular events. The relationship between disease progression and outcomes largely reflected the need for coronary revascularization. These data support the use of atherosclerosis imaging with IVUS in the evaluation of novel antiatherosclerotic therapies.