Independent risk factors for mortality in patients with chronic obstructive pulmonary disease who undergo comprehensive cardiac evaluations.

BACKGROUND: Cardiovascular disease is the most common cause of death in chronic obstructive pulmonary disease (COPD). However, the impact of cardiovascular comorbidities on the prognosis of COPD is not well known. OBJECTIVES: This study was performed to investigate the effects of cardiovascular comorbidities on the prognosis of COPD. METHODS: We enlisted 229 patients with COPD who underwent comprehensive cardiac evaluations including coronary angiography and echocardiography at Ajou University Hospital between January 2000 and December 2012. Survival analyses were performed in this retrospective cohort. RESULTS: Kaplan-Meier analyses showed that COPD patients without left heart failure (mean survival = 12.5 ± 0.7 years) survived longer than COPD patients with left heart failure (mean survival = 6.7 ± 1.4 years; p = 0.003), and the survival period of nonanemic COPD patients (mean survival = 13.8 ± 0.8 years) was longer than that of anemic COPD patients (mean survival = 8.3 ± 0.8 years; p < 0.001). The survival period in COPD with coronary artery disease (CAD; mean survival = 11.37 ± 0.64 years) was not different from that in COPD without CAD (mean survival = 11.98 ± 0.98 years; p = 0.703). According to a multivariate Cox regression model, a lower hemoglobin level, a lower left ventricular ejection fraction, and the forced expiratory volume in 1 s (FEV1) were independently associated with higher mortality in the total COPD group (p < 0.05). CONCLUSIONS: Hemoglobin levels and left ventricular ejection fraction along with a lower FEV1 were identified as independent risk factors for mortality in COPD patients who underwent comprehensive cardiac evaluations, suggesting that multidisciplinary approaches are required in the care of COPD.

The relationship between intravascular ultrasound-derived percent total atheroma volume and fractional flow reserve in the intermediate stenosis of proximal or middle left anterior descending coronary artery.

BACKGROUND: It remains undefined whether the atherosclerotic disease extent of the conductive vessel (expressed as intravascular ultrasound [IVUS]-derived percent total atheroma volume [%TAV]), correlates with functional severity of intermediate stenosis of left anterior descending artery (LAD). METHODS: An IVUS study and fractional flow reserve (FFR) measurements performed in 130 patients with coronary angiographic intermediate stenosis of proximal or middle LAD. %TAV was calculated as the percentage of total vessel volume occupied by total atheroma volume on IVUS. RESULTS: A significant correlation was observed between %TAV and FFR (r=-0.71, p<0.001). Minimal lumen area (MLA) correlated moderately with FFR (r=0.54, p<0.001). The independent predictors of FFR<0.8 were %TAV (odds ratio [OR]: 1.29, 95% confidence interval [CI]=1.18-1.40, p<0.001) and MLA (OR: 0.37, 95% CI=0.16-0.85, p=0.019). A receiver-operating characteristic curve suggested %TAV ≥ 39.0% (sensitivity 85%, specificity 83% and area under curve [AUC]=0.90) and MLA ≤ 2.6mm(2) (sensitivity 72%, specificity 70% and AUC=0.75) as the best cut-off values for FFR<0.8. Forty-eight point five (48.5%) of total studied lesions (63/130) showed %TAV ≥ 39.0%. Eighty-four point four (84.4%) of lesions (38/45) with %TAV ≥ 39.0% and MLA ≤ 2.6mm(2), and 72.2% of lesions (13/18) with %TAV ≥ 39.0% and MLA>2.6mm(2), FFR was less than 0.8. CONCLUSIONS: Volumetric quantification of the atherosclerotic disease extent of the coronary artery, expressed as IVUS-derived %TAV, showed a strong correlation with FFR. Not only the segmental luminal narrowing but also the total plaque burden of conductive artery are major determinants for the presence of myocardial ischemia in intermediate stenosis of LAD.

Point-of-care measurements of platelet inhibition after clopidogrel loading in patients with acute coronary syndrome: comparison of generic and branded clopidogrel bisulfate.

PURPOSE: Platelet-function suppression with antiplatelet therapy is effective in preventing and treating cardiovascular disease. Clopidogrel is a thienopyridine derivative that blocks platelet activation by adenosine diphosphate receptor binding. This study demonstrates the effects of generic clopidogrel bisulfate in comparison to branded clopidogrel bisulfate in patients with acute coronary syndromes. METHODS: This prospective, 2-arm, single-center, open-label trial used 1:1 randomization to assign patients to receive generic or branded clopidogrel bisulfate. Patients with unstable angina or non-ST-segment elevation myocardial infarction and scheduled to undergo coronary angiography were enrolled. Platelet function was measured with a P2Y12 assay and reported in P2Y12 reaction units (PRU) and aspirin reaction units (ARU) after randomization. Platelet function was measured at 2, 4, 8, and 24 hours after 600-mg clopidogrel loading. The clinical outcome was checked at 1 month after coronary angiography. FINDINGS: Ninety-five patients were enrolled and randomized to the generic or branded group. Ninety patients (62 men [69%], 28 women [31%]; mean age, 58 years) completed the study protocol. The clinical characteristics were similar between the 2 groups. The difference in the baseline PRU measurements between the generic and branded groups was not significant (274.8 [59.7] vs 285.4 [62.4], respectively; P = 0.414). There were significant differences in 2-hour PRU (231.1 [71.3] vs 266.9 [67.4]; P = 0.017) and 4-hour PRU (227.3 [80.4] vs 265.7 [71.0]; P = 0.020); however, 24-hour PRU (200.5 [82.1] vs 220.6 [75.8]; P = 0.253) was similar. No death, myocardial infarction, target lesion revascularization, stent thrombosis, or Thrombolysis in Myocardial Infarction-defined major bleeding complications were reported during in-hospital stay or 1-month follow-up. IMPLICATION: In patients with ACS, loading of generic clopidogrel bisulfate was associated with an antiplatelet effect comparable to that of branded clopidogrel bisulfate. ClinicalTrials.gov identifier: NCT02060786.

Relationship between intravascular ultrasound parameters and fractional flow reserve in intermediate coronary artery stenosis of left anterior descending artery: intravascular ultrasound volumetric analysis.

OBJECTIVES: The objective of this study was to assess the relationship between intravascular ultrasound (IVUS) parameters, including volumetric analysis, and fractional flow reserve (FFR). BACKGROUND: Although it is known that coronary atherosclerosis burden measured by IVUS volumetric analysis is related with clinical outcomes, its relationship with functional significance remains unknown. METHODS: Both IVUS and FFR were performed in 206 cases of intermediate stenosis of the left anterior descending artery (LAD). Myocardial ischemia was assessed by FFR and maximal hyperemia was induced by continuous intracoronary adenosine infusion. FFR < 0.80 was considered as significant inducible myocardial ischemia. We performed standard IVUS parameter measurements and volumetric analyses. IVUS parameter comparison was performed in the presence (n = 90) or absence (n =116) of significant myocardial ischemia. RESULTS: Lesions with minimal lumen area (MLA) ≥ 4.0 mm2 had FFR ≥ 0.80 in 91.4% of cases, while 50.9% of lesions with MLA < 4.0 mm2 had FFR < 0.80. The independent predictors of FFR < 0.80 were IVUS lesion length (odds ratio [OR]: 1.1, 95% confidence interval [CI] = 1.06­1.18, P < 0.001) and MLA significance according to the lesion location (OR: 7.01, 95% CI = 3.09­15.92, P = 0.001). FFR correlated with plaque volume (r = −0.345, P < 0.001) and percent atheroma volume (PAV) (r = −0.398, P < 0.001). Lesions with significant ischemia (FFR < 0.80) as compared to those with FFR > 0.80 were associated with larger plaque volume (181.8 ± 82.3 vs. 125.9 ± 77.9 mm3, P < 0.001) and PAV (58.9 ± 5.6 vs. 53.8 ± 7.9%, P < 0.001). CONCLUSIONS: IVUS parameters representing severity and extent of atheromatous plaque correlated with functional significance in LAD lesions with intermediate stenosis.

Comparison of 3-year clinical outcomes between classic crush and modified mini-crush technique in coronary bifurcation lesions.

OBJECTIVES: We aimed to compare long-term clinical outcomes between modified mini-crush (modi-MC) technique with classic crush (crush) technique for treatment of bifurcation lesions. BACKGROUND: The modi-MC technique showed excellent procedural success and favorable 9-month clinical outcomes. METHODS: From January 2005 to November 2009, we enrolled patients with de novo bifurcation lesions treated with modi-MC (n = 112 lesions in 111 patients) and crush technique (n = 69 lesions in 67 patients). Primary endpoint was rate of major adverse cardiac events (MACE), a composite of all-cause death, myocardial infarction (MI), and target lesion revascularization (TLR) at 3 years. RESULTS: There was no significant difference in baseline characteristics. The modi-MC technique showed a significantly higher success rate of final kissing balloon inflation (84.1 vs. 98.2%, P = 0.001). After 3 years, MACE rate was significantly lower in the modi-MC group (25.4 vs. 12.6%, P = 0.030). The incidence of all-cause death was 7.5 vs. 2.7% (P = 0.087), MI was 4.5 vs. 1.8% (P = 0.290), TLR was 17.4 vs. 8.9% (P = 0.093) and stent thrombosis was 3.0 vs. 1.8% (P = 0.632) in the crush and modi-MC groups, respectively. CONCLUSIONS: The modified mini-crush technique showed more favorable 3-year clinical outcomes compared to the classic crush technique.

[Mitochondrial DNA mutations in lung cancer].

BACKGROUND AND OBJECTIVE: Mitochondiral DNA (mtDNA) mutations has been identified in various cancers, but their significance was unknown. This study aimed to detect mtDNA mutations in lung cancer, and to investigate their roles in the carcinogenesis of human lung. METHODS: Total DNA (including nuclear DNA and mtDNA) was extracted from the tumor tissues, corresponding distal non-cancerous lung tissues, and peripheral lymphocytes derived from 58 patients with lung cancer. Fifty-eight overlapping fragments and covering complete sequence of mtDNA were amplified by nested PCR, and the PCR products were sequenced directly with the cycle sequencing methods. The mtDNA mutations in the tumor tissue were determined by comparing with corresponding and peripheral lymphocytes. RESULTS: Sixty-six mutations were identified in 36 cases (62.1%) of lung cancer, including 58 point mutations, 4 insertions, and 4 deletions. These mutations were dispersedly distributed in the full length of mtDNA. The frequency of mutation in D-loop is the highest, in which 18 mutations were detected. No mutation hot spot was found in peptide-coding regions. Among 43 point mutations identified in protein-coding region, 20 were silent mutations. In 8 patients, identical mutations were detected both in the tumor tissues and corresponding distal non-cancerous tissues. CONCLUSION: Most of mtDNA mutations in the lung cancers investigated were occurred randomly and might have no impact on carcinogenesis; whereas the homoplasmic mutations may provide a potential diagnostic marker for lung cancer.