Fifteen-Year Nationwide Trend in Antiplatelet Treatment among Drug-Eluting Stent Recipients in Korea: Many Patients Receive Very Prolonged Dual-Antiplatelet Treatment, and Newer Drugs Are Replacing the Older Ones.

Drug-eluting stent (DES) recipients require 6-12 months of dual antiplatelet treatment (DAPT) and long-term aspirin mono-antiplatelet treatment (MAPT). Given the diversity of contemporary antiplatelet agents, antiplatelet treatment (APT) selection is becoming more complicated. We evaluated 15-year APT trends based on nationwide prescription data of 79,654 patients who underwent percutaneous coronary intervention (PCI) using DESs from 2002 to 2018 in Korea. DAPT (80.7%) was the most preferred initial APT post-PCI. Many DES recipients received prolonged DAPT (post-PCI 3 years: 41.0%; 10 years: 27.7%). There was a noticeable delay in DAPT-to-MAPT conversion from the mid to late 2000s (after the late-stent thrombosis concerns of first-generation DESs raised); the conversion after that was similar during the 2010s, occurring most robustly at 12-18 months post-PCI. Clopidogrel had long and increasingly been used for MAPT, surpassing aspirin. The recent increase in newer P2Y12 inhibitor prescriptions was noted. The patients treated with newer P2Y12 inhibitors were more likely younger men and presented with acute myocardial infarction. Real-world APT is evolving, and guideline-practice gaps exist. Further studies exploring the impact of diverse APT strategies on patient outcomes are expected to provide insights into optimal APT that can sophisticatedly balance the ischemic and bleeding risks.

Favorable Vasomotor Function after Drug-Coated Balloon-Only Angioplasty of De Novo Native Coronary Artery Lesions.

Balloon-injured coronary segments are known to harbor abnormal vasomotion. We evaluated whether de novo coronary lesions treated using drug-coated balloon (DCB) are prone to vasospasm and how they respond to ergonovine and nitrate. Among 132 DCB angioplasty recipients followed, 89 patients underwent ergonovine provocation test at 6-9 months follow-up. Within-subject ergonovine- and nitrate-induced diameter changes were compared among three different sites: DCB-treated vs. angiographically normal vs. segment showing prominent vasoreactivity (spastic). No patient experienced clinically refractory vasospastic angina or symptom-driven revascularization during follow-up. Ergonovine induced vasospasm in seven patients; all were multifocal spasm either involving (n = 2) or rather sparing DCB-treated segments (n = 5). None showed focal spasm that exclusively involved DCB-treated lesions. Among 27 patients with vasospastic features, DCB-treated segments showed less vasoconstriction than spastic counterparts (p < 0.001). A total of 110 DCB-treated lesions were analyzed to assess vasomotor function. Vasomotor function, defined as a combined constrictor and dilator response, was comparable between DCB-treated and angiographically normal segments (p = 0.173), while significant differences were observed against spastic counterparts (p < 0.001). In our study, DCB-treated lesions were not particularly vulnerable to vasospasm and were found to have vasomotor function similar to angiographically normal segments, supporting safety of DCB-only strategy in treating de novo native coronary lesions.

Clinical and central hemodynamic characteristics of early adulthood isolated diastolic hypertension: a comparison with isolated systolic hypertension.

OBJECTIVES: Knowledge on early adulthood isolated diastolic hypertension (IDH) is limited. We compared the clinical and central hemodynamic characteristics of early adulthood IDH, isolated systolic hypertension (ISH) and normotension. METHODS: A total of 509 untreated young adults (18-35 years) who underwent ambulatory blood pressure monitoring (ABPM; ABPM cohort), 148 who underwent both ABPM and applanation tonometry (ABPM-tonometry cohort) and 26 newly recruited normotensives were analyzed. Their pulse wave images were analyzed after categorizing them into type A vs. B vs. C. RESULTS: In the ABPM cohort (men, 86.6%), systolic-diastolic hypertension was the most common subtype (68.0%), while IDH was the rarest (5.1%). The subtype composition showed age-dependency; the proportion of IDH and systolic-diastolic hypertension increased across the age tertiles, while that of ISH declined. Patients with IDH were significantly older and shorter than those with ISH. Despite having a significantly lower 24-h average systolic blood pressure (SBP), patients with IDH exhibited discordantly high central systolic blood pressures at levels comparable to those of patients with ISH. Pulse pressure amplification was the lowest in patients with IDH and highest in those with ISH (P < 0.001), accounting for the discordance. Augmentation index differed significantly between them (P < 0.016). The waveform composition differed across the subtypes (type A vs. B/C: IDH = 61.5 vs. 38.5%; ISH = 3.0 vs. 97.0%; normotension = 30.8 vs. 69.2%, P < 0.001); the averaged waveform plots demonstrated a clear morphological disparity between IDH (type A) and ISH (type B/C). CONCLUSIONS: Early adulthood IDH is a unique entity clearly distinguishable from ISH in terms of clinical and central hemodynamic characteristics.

Efficacy and safety of co-administered telmisartan/amlodipine and rosuvastatin in subjects with hypertension and dyslipidemia.

Single risk factors, such as hypertension and dyslipidemia, can combine to exacerbate the development and severity of cardiovascular disease. Treatment goals may be more effectively achieved if multiple disease factors are targeted with combination treatment. We enrolled 202 patients who were randomly divided into the following three groups: telmisartan/amlodipine 80/5 mg + rosuvastatin 20 mg, telmisartan 80 mg + rosuvastatin 20 mg, and telmisartan/amlodipine 80/5 mg. The primary efficacy variables were changes from baseline in mean sitting systolic blood pressure (MSSBP) between telmisartan/amlodipine 80/5 mg + rosuvastatin 20 mg and telmisartan 80 mg + rosuvastatin 20 mg at 8 weeks, and the percent changes from baseline in low-density lipoprotein (LDL) cholesterol between telmisartan/amlodipine 80/5 mg + rosuvastatin 20 mg and telmisartan/amlodipine 80/5 mg at 8 weeks. The secondary efficacy variables were changes in MSSBP, mean sitting diastolic blood pressure (MSDBP), LDL cholesterol and other lipid levels at 4 weeks and 8 weeks, as well as observed adverse events during follow-up. There were no significant differences between the three groups in demographic characteristics and no significant difference among the three groups in terms of baseline characteristics for the validity evaluation variables. The mean overall treatment compliance in the three groups was, respectively, 98.42%, 96.68%, and 98.12%, indicating strong compliance for all patients. The Least-Square (LS) mean (SE) for changes in MSSBP in the two (telmisartan/amlodipine 80/5 mg + rosuvastatin 20 mg and telmisartan 80 mg + rosuvastatin 20 mg) groups were -19.3 (2.68) mm Hg and -6.69 (2.76) mm Hg. The difference between the two groups was significant (-12.60 (2.77) mm Hg, 95% CI -18.06 to -7.14, P < .0001). The LS Mean for the percent changes from baseline in LDL cholesterol in the two (telmisartan/amlodipine 80/5 mg + rosuvastatin 20 mg and telmisartan/amlodipine 80/5 mg) groups were -52.45 (3.23) % and 2.68 (3.15) %. The difference between the two groups was significant (-55.13 (3.20) %, 95% CI -61.45 to -48.81, P < .0001). There were no adverse events leading to discontinuation or death. Combined administration of telmisartan/amlodipine 80/5 mg and rosuvastatin 20 mg for the treatment of hypertensive patients with dyslipidemia significantly reduces blood pressure and improves lipid control. ClinicalTrials.gov identifier: NCT03067688.

A randomized, double-blind clinical trial to evaluate the efficacy and safety of a fixed-dose combination of amlodipine/rosuvastatin in patients with dyslipidemia and hypertension.

This multicenter, randomized, double-blind, parallel-group phase III clinical trial aimed to investigate the efficacy and safety of a rosuvastatin + amlodipine combination compared with that of rosuvastatin or amlodipine monotherapy in hypertensive patients with dyslipidemia. A total of 106 patients of 15 institutions in Korea were randomly assigned to 1 of 3 treatment groups: rosuvastatin 20 mg + amlodipine 10 mg, amlodipine 10 mg, or rosuvastatin 20 mg. After 8 weeks of treatment, the mean ± SD of change in mean sitting systolic blood pressure (msSBP) was -22.82 ± 12.99 mm Hg in the rosuvastatin + amlodipine group, the most decreased among the treatment groups. The percentage of patients whose msSBP decreased ≥20 mm Hg or msDBP decreased ≥10 mm Hg was also highest in this group (74.29%). The mean ± SD percentage change in low-density lipoprotein cholesterol (LDL-C) level from baseline after 8 weeks was -52.53% ± 11.21% in the rosuvastatin + amlodipine group, the most decreased among the treatment groups. More patients in the rosuvastatin + amlodipine group achieved their target LDL-C goal at 8 weeks, compared with the other treatment groups (97.14%). No serious adverse events or adverse drug reactions were observed in all groups. In hypertensive patients with dyslipidemia, combination treatment with rosuvastatin 20 mg + amlodipine 10 mg effectively reduced blood pressure and LDL-C levels while maintaining safety.

Central hemodynamic characteristics of young adults with isolated systolic hypertension: an ambulatory blood pressure monitoring-based study of real-world clinical patients.

The central hemodynamic characteristics of young adults with isolated systolic hypertension (ISH) remain controversial, particularly regarding the extent of pulse pressure amplification (PPamp) compared with that of normotensives (NTs). Given the lack of ambulatory blood pressure monitoring (ABPM)-based data, this study evaluated 509 untreated young adults (18-35 years) who had undergone ABPM during the last decade, 109 who had undergone both ABPM and SphygmoCor analysis, and 26 newly recruited NTs. The agreement rate between office BP- and ABPM-based subtype classification was alarmingly low (50.7%). ISH was distinguishable from systolic-diastolic hypertension, the predominant subtype characterized by increased central BPs and stiffened arteries. The central hemodynamic parameters were all similar between patients with ISH and white-coat hypertension (WC). ISH patients had central BPs that were, albeit higher than those of NTs, at an upper-normal level that was comparable to those of WC patients. ISH patients had similar cfPWV but significantly higher PPamp than NTs (p = 0.032). The central hemodynamic parameters of the participants were further analyzed according to central pressure waveform types (A vs. B vs. C). Type C waves were associated with the highest PPamp and lowest cfPWV, whereas type A waves were associated with the lowest PPamp and highest cfPWV. Subjects with type B waves, an intermediate form, also had considerably high PPamps. Waveform composition differed significantly across hypertension subtypes (p < 0.001). ISH patients mostly had type B or C waves (96.7%), with only 3.3% having type A waves. This study based on a refined diagnosis showed that the ambulatory ISH of young adults arises from highly elastic arteries and related robustness of PPamp and shares similar central hemodynamic characteristics with WC patients.

Efficacy and Safety of a Fixed-Dose Combination of Candesartan and Rosuvastatin on Blood Pressure and Cholesterol in Patients With Hypertension and Hypercholesterolemia: A Multicenter, Randomized, Double-Blind, Parallel Phase III Clinical Study.

PURPOSE: The aim of this study was to evaluate the blood pressure-lowering and cholesterol-lowering effects of a fixed-dose combination therapy using candesartan (CND)/rosuvastatin (RSV) compared with CND or RSV monotherapy in patients with hypertension and hypercholesterolemia. METHODS: This study was a 12-week, randomized, double-blind, placebo-controlled, multicenter study. A total of 394 patients were screened. After a 4-week run-in period, 219 of these patients with hypertension and primary hypercholesterolemia were randomized. Patients received 1 of 3 regimens for 8 weeks: (1) CND 32 mg/RSV 20 mg, (2) RSV 20 mg, or (3) CND 32 mg. The primary outcome variables were changes in the systolic blood pressure (SBP) and diastolic blood pressure (DBP) and the percentage changes in LDL-C from baseline to the drug treatment at 8 weeks. The secondary outcome variables were percentage changes of total cholesterol, triglycerides, HDL-C, non-HDL-C, apolipoprotein B, apolipoprotein A-I, high-sensitivity C-reactive protein, and glucose metabolic indices, including percentage changes of the homeostasis model assessment of insulin resistance (HOMA-IR), adiponectin, and hemoglobin A1c. Tolerability of combination therapy was compared with other monotherapy groups. FINDINGS: The percentage changes of LDL-C were -48.6% (from 157.2 to 80.1 mg/dL) in the RSV group and -49.8% (from 160.2 to 78.9 mg/dL) in the CND/RSV group from baseline to the end of 8 weeks of treatment. Mean SBP and DBP were significantly decreased in the CND/RSV and CND groups after 8 weeks (P < 0.001 for all); however, no significant differences were found between the 2 groups. Total cholesterol levels, triglycerides, non-HDL-C, and apolipoprotein B were significantly reduced in the CND/RSV and RSV groups, with no significant differences between the groups compared with the CND group (P < 0.001 for all). The percentage changes of HOMA-IR, adiponectin, and hemoglobin A1c had no significant differences between the combination groups and monotherapy groups. However, in a 2-sample t test, HOMA-IR was significantly decreased in the CND/RSV group compared with the RSV group in nondiabetic patients (mean [SD] percentage change of HOMA-IR, -8.7% [37.6%] vs 17.1% [53.1%]; P = 0.048). There were no significant differences in metabolic indices between the diabetic groups. Adverse events in the CND/RSV group were similar to those in the monotherapy group. IMPLICATIONS: Once-daily fixed-dose combination therapy with CND/RSV is an effective, tolerable, convenient treatment option for patients with essential hypertension and hypercholesteremia. ClinicalTrials.gov identifier: NCT02770261.

Efficacy and Tolerability of Telmisartan/Amlodipine and Rosuvastatin Coadministration in Hypertensive Patients with Hyperlipidemia: A Phase III, Multicenter, Randomized, Double-blind Study.

PURPOSE: Dyslipidemia and hypertension increase the risk for cardiovascular disease. Combination therapy improves patient compliance. This study was conducted to compare the efficacy and tolerability of the combination therapies telmisartan/amlodipine + rosuvastatin, telmisartan/amlodipine, and telmisartan + rosuvastatin in patients with hypercholesterolemia and hypertension. METHODS: In this Phase III, multicenter, 8-week randomized, double-blind study, participants with hypertension and dyslipidemia (defined as a sitting systolic blood pressure [sitSBP] of ≥140 mm Hg, a low-density lipoprotein-cholesterol [LDL-C] level of ≤250 mg/dL, and a triglyceride level of ≤400 mg/dL) were screened. After a 4-week washout/run-in period involving therapeutic lifestyle changes and telmisartan 80 mg once a day, eligible patients had a sitSBP of ≥140 mm Hg and met the LDL-C level criteria according to the National Cholesterol Education Program Adult Treatment Panel III cardiovascular disease risk category. Patients were randomly assigned to 1 of 3 groups: (1) telmisartan/amlodipine 80/10 mg + rosuvastatin 20 mg (TAR group); (2) telmisartan/amlodipine 80/10 mg (TA group); or (3) telmisartan 80 mg + rosuvastatin 20 mg (TR group). The primary efficacy end points were the percentage changes from baseline in LDL-C in the TAR and TA groups and the mean changes in sitSBP in the TAR and TR groups at week 8 compared to baseline. Continuous variables were compared using the unpaired t test or the Wilcoxon rank sum model, and categorical variables were compared using the χ2 or Fisher exact test. Tolerability was assessed based on adverse events found on physical examination including vital sign measurements, laboratory evaluations, and 12-lead ECG. FINDINGS: A total of 134 patients were enrolled. The least squares mean percentage changes in LDL-C at 8 weeks after administration of the drug compared to baseline were -51.9% (3.0%) in the TAR group and -3.2% (2.9%) in the TA group (P < 0.001). At 8 weeks after baseline, the least squares mean (SE) changes sitSBP were -28.3 (2.4) mm Hg in the TAR group and -10.7 (2.1) mm Hg in the TR group (P < 0.001). The prevalence rates of treatment-emergent adverse events were 15.0%, 25.0%, and 12.2% in the TAR, TA, and TR groups, respectively; those of adverse drug reactions were 15.0%, 22.7%, and 10.2%. None of the differences in rates were significant among 3 groups. IMPLICATIONS: Triple therapy with TAR can be an effective treatment in patients with dyslipidemia and hypertension. The TAR combination has value for hypertensive patients with hyperlipidemia in terms of convenience, tolerability, and efficacy. ClinicalTrials.gov identifier: NCT03566316.

Irreversible effects of long-term chronic smoking on arterial stiffness: An analysis focusing on ex-smokers among otherwise healthy middle-aged men.

Objective: Smoking is a modifiable cardiovascular risk factor closely related to arterial stiffness (AS). However, data are lacking regarding the chronic effects of smoking on AS, especially in ex-smoker (ES) who faces remnant cardiovascular risk when compared to never-smokers (NS).Methods: Among 1722 health screening participants, we retrospectively evaluated 652 healthy men with different smoking history [240 current smoker (CS) vs. 228 ES vs. 184 NS]. To assess AS, augmentation index (AIx), pulse pressure amplification (PPamp), and carotid-femoral pulse wave velocity (cfPWV) were measured and compared.Results: Baseline characteristics were similar except age and triglyceride level. AIx was lowest in NS, followed by ES, and was highest in CS. PPamp was highest in NS, lowest in CS, and ES was of intermediate level. The differences were more robust after adjustment for baseline covariates (AIx, p = 0.005; PPamp: p = 0.001). On the other hand, no significant intergroup difference was observed for cfPWV in our middle-aged population. With the regression analyses revealing an independent association between smoking duration and AS in ES, subgroup analysis demonstrated that long-term ES (smoking duration ≥20 years) had significantly higher AS than short-term ES (<20 years) and NS, approaching levels comparable to CS (AIx and PPamp: p < 0.0001).Conclusions: Our study demonstrated impaired arterial elastic properties in long-term ES, suggesting that AS caused by chronic smoking might be irreversible even after smoking cessation. Further longitudinal studies are warranted to determine the impacts of past smoking on AS and its clinical relevance.

Efficacy and Tolerability of Telmisartan/Amlodipine + Hydrochlorothiazide Versus Telmisartan/Amlodipine Combination Therapy for Essential Hypertension Uncontrolled With Telmisartan/Amlodipine: The Phase III, Multicenter, Randomized, Double-blind TAHYTI Study.

PURPOSE: This 8-week study in Korea aimed to evaluate the efficacy and tolerability of a telmisartan/amlodipine + hydrochlorothiazide (TAH) combination versus telmisartan/amlodipine (TA) combination in patients with essential hypertension that did not respond appropriately to 4-week treatment with TA. METHODS: All patients who met the inclusion criteria received TA (40/5 mg) during a 4-week run-in period (period 1). Patients who met the criteria for essential hypertension (mean sitting systolic blood pressure [MSSBP], ≥140 and <200 mm Hg, or ≥130 and<200 mm Hg in those with diabetes mellitus or chronic kidney disease) after period 1 were randomly assigned to receive TA 40/5 mg + hydrochlorothiazide 12.5 mg (test group) or TA only (control group). The test and control drugs were administered in each group for 2 weeks (period 2). Patients who completed period 2 underwent 6-week treatment (period 3) with a TAH and TA dose twice that in period 2. The primary end point was the change in MSSBP at week 8 of treatment. Secondary end points were the change in MSSBP at week 2 and MS diastolic BP, BP control rate, and BP response rate at weeks 2 and 8. Treatment tolerability was assessed based on adverse events (AEs), laboratory evaluations (chemistry, hematology, and urinalysis), 12-lead ECG, and physical examination including vital sign measurements. FINDINGS: We randomized 310 patients to the treatment groups. The mean (SD) ages of the TAH and TA groups were 62.0 (10.8) and 63.4 (10.4) years, respectively. The least squares mean change in MSSBP was significantly greater in the TAH group than in the TA group after 8 weeks (-18.7 vs -12.2 mm Hg; P < 0.001). Similar results were obtained on changes in MSSBP after 2 weeks and changes in sitting diastolic BP, BP control rate, and BP response rate at weeks 2 and 8 compared with the respective baseline values. The prevalences of treatment-emergent AEs (29.0% vs 16.3%; P = 0.008) and adverse drug reactions (20.0% vs 10.5%; P = 0.020) were significantly greater in the TAH group than in the TA group. Most treatment-emergent AEs were mild or moderate; none were severe. The most frequently reported AEs were dizziness and headache. IMPLICATION: TAH triple therapy was more effective than was TA double therapy in reducing BP in these patients in Korea with essential hypertension that did not adequately respond to TA. ClinicalTrials.gov identifier: NCT02738632.

Inferior vena cava collapsibility index, renal dysfunction, and adverse outcomes in patients with broad spectrum cardiovascular disease.

AIMS: The clinical implication of the inferior vena cava collapsibility index (IVCCI) has not been well evaluated in patients with various cardiovascular diseases. METHOD AND RESULTS: The relationships between clinical characteristics and echocardiographic indicators of the systemic intravascular volume status [IVCCI; the ratio of the early transmitral and early myocardial diastolic velocities (E/Em)] were evaluated at baseline, and the clinical status during follow-up was compared across the IVCCI levels. Among 1166 patients (mean age=63.8±13.4 years), 934, 171, and 61 had high (≥50%), intermediate (25%-50%), and low (<25%) IVCCIs, respectively. Age-, sex-, and body mass index-adjusted serum creatinine (sCr) levels were highest in patients with low IVCCI (P=.002) and E/Em >15 (P<.001). During follow-up (1108±463 days), 67 patients died, and 38 of these deaths were cardiovascular related. Age, body mass index, heart failure (HF), sCr levels, and a low IVCCI (vs high IVCCI: hazard ratio [HR]=3.193, 95% confidence interval [CI]=1.297-7.857, P=.012) were associated with all-cause mortality in multivariable analysis. HF, diuretic use, and a low IVCCI (vs high IVCCI: HR=4.428, 95% CI=1.406-13.104, P=.007) were significantly associated with cardiovascular mortality. CONCLUSION: A low IVCCI was significantly associated with reduced renal function and was an independent risk factor for adverse outcomes, regardless of underlying cardiovascular disease and renal function.

Evaluation of the Efficacy and Safety of the Lercanidipine/Valsartan Combination in Korean Patients With Essential Hypertension Not Adequately Controlled With Lercanidipine Monotherapy: A Randomized, Multicenter, Parallel Design, Phase III Clinical Trial.

PURPOSE: The objective of this study was to evaluate the efficacy and safety of the lercanidipine/valsartan combination compared with lercanidipine monotherapy in patients with hypertension. METHODS: Part 1 of this study was the randomized, multicenter, double-blind, parallel group, Phase III, 8-week clinical trial to compare superiority of lercanidipine 10 mg/valsartan 80 mg (L10/V80) and lercanidipine 10 mg/valsartan 160 mg (L10/V160) combinations with lercanidipine 10 mg (L10) monotherapy. At screening, hypertensive patients, whose diastolic blood pressure (DBP) was >90 mm Hg after 4 weeks with L10, were randomized to 3 groups of L10, L10/V80, and L10/V160. The primary end point was the change in the mean sitting DBP from baseline (week 0) after 8 weeks of therapy. Patients who were randomly assigned to L10/V160 and whose mean DBP was still ≥ 90 mm Hg in part 1 were enrolled to the up-titration extension study with lercanidipine 20 mg/valsartan 160 mg (L20/V160) (part 2). FINDINGS: Of 772 patients screened, 497 were randomized to 3 groups (166 in the L10 group, 168 in the L10/V80 group, and 163 in the L10/V160 group). Mean (SD) age was 55 (9.9) years, and male patients comprised 69%. The mean (SD) baseline systolic blood pressure (SBP)/DBP were 148.4 (15.1)/94.3 (9.5) mm Hg. No significant differences were found between groups in baseline characteristics except the percentages of previous history of antihypertensive medication. The primary end points, the changes of mean (SD) DBP at week 8 from the baseline were -2.0 (8.8) mm Hg in the L10 group, -6.7 (8.5) mm Hg in L10/V80 group, and -8.1 (8.4) mm Hg in L10/V160 group. The adjusted mean difference between the combination groups and the L10 monotherapy group was -4.6 mm Hg (95% CI, -6.5 to -2.6; P < 0.001) in the L10/V80 group and -5.9 mm Hg (95% CI, -7.9 to -4.0, P < 0.001) in the L10/V160 group, which had significantly greater efficacy in BP lowering. A total of 74 patients were enrolled in the part 2 extension study. Changes of mean (SD) DBP and SBP from week 8 to week 12 and week 16 were -5.6 (7.9)/-8.0 (12.0) mm Hg and -5.5 (7.0)/-8.5 (11.3) mm Hg, respectively. For evaluation of the safety profile, the frequencies of adverse events between groups were also not significantly different. The most frequently reported adverse events were headache (6 cases, 20.7%) in the L10 group, dizziness (8 cases, 16.3%) in L10/V80 group, and nasopharyngitis (3 cases, 9.4%) in L10/V160 group, and the incidences of adverse events were not different between groups. IMPLICATIONS: Treatment of L10/V80 or L10/V160 combination therapy resulted in significantly greater BP lowering compared with L10 monotherapy. Moreover, the L20/V160 high dose combination had additional BP lowering effect compared with nonresponders with the L10/V160 combination. ClinicalTrials.gov: NCT01928628.

Patterns of decrease in multidirectional myocardial deformations in patients with fluctuating left ventricular ejection fraction.

Few studies have examined the variations in longitudinal/circumferential/radial strain (LS/CS/RS) and strain rate (LSr/CSr/RSr) in individual hearts when the left ventricular ejection fraction (LVEF) has changed. We hypothesized the relationships of strain/strain rate and LVEF are not linear, but vary with multiple inflection points (IPs) in individual hearts.Twenty-five patients with fluctuating LVEF (ΔLVEF > 10%) who had 2-D speckle tracking echocardiography available for analysis were enrolled. After models of best fit were obtained from the 'collective' plots to determine inflection points, the decrements of slopes above inflection points (IP) were compared with those below IPs in the 'individual hearts' plots.In the 'collective' plots, both LS and LSr linearly decreased in proportion to LVEF when LVEF ≥ 40% but remained constant regardless of LVEF when LVEF < 40% (IPs when LVEF = 40%, P < 0.0001). The RS-LVEF relationship was sigmoid with two IPs when LVEF = 30% and 50% (P < 0.0001). However, in the 'individual hearts' plots, the decrements of slopes above and below IPs were not different for LS-LVEF and LSr-LVEF, and marginally different for RS-LVEF (P = 0.049, across IP when LVEF = 50%).Collectively, the relationship of LS/LSr/RS and LVEF seemed to be not linear, but inflective, however, we could not prove the inflective relationship in individual hearts with fluctuating LVEF. Further study with more patients is needed to prove our hypothesis.

Primary cardiac lymphoma presenting as an atypical type of hypertrophic cardiomyopathy.

Primary cardiac lymphoma (PCL) is a very rare malignancy although cardiac involvement with the disseminated disease is not uncommon. We present a case of a 43-year-old man with PCL that initially presented as marked thickening of all cardiac walls and was mistakenly diagnosed as an atypical type of hypertrophic cardiomyopathy. The diagnosis of PCL was made with a delay of 9 months after the initial presentation, when atypical lymphocytes staining positive for CD79a and CD20 were demonstrated in the rapidly growing mediastinal and neck mass. Anthracycline-based chemotherapy and anti-CD20 immunotherapy resulted in a remarkable reduction in cardiac wall thickness and mediastinal mass. The first lesson to be learnt from this case is that PCL can present as a diffuse infiltrative disease without a mass. The second lesson is that prompt exploratory thoracotomy should not be delayed when the diagnosis is elusive.

Discordant impairment of multidirectional myocardial deformation in rats with Doxorubicin induced cardiomyopathy.

BACKGROUND: In doxorubicin-induced cardiomyopathy (DIC), the sequence of decrease in multidirectional myocardial deformation has not been clearly elucidated. OBJECTIVES: We investigated the sequence of myocardial deformations in rat DIC, using two-dimensional speckle tracking echocardiography (2DSTE). METHODS: Twenty rats were treated with doxorubicin (1.25 mg/kg × 16 times, intraperitoneal) for 4 weeks and compared with nine control rats. Myocardial strain analysis with 2DSTE, as well as conventional echocardiography, was obtained. RESULTS: Compared with baseline, longitudinal strain/strain rate (LS/LSr) decreased at week 2 (-15.7 ± 1.5 to -14.1 ± 1.4%, P = 0.01 for LS; -4.4 ± 0.7 to -3.9 ± 0.5 per second, P = 0.009 for LSr). Left ventricular ejection fraction (LVEF) and circumferential strain (CS) decreased at week 4 (80.3 ± 3.2 to 78.1 ± 3.3%, P = 0.031 for LVEF; -18.6 ± 1.9 to -15.0 ± 3.4%, P = 0.019 for CS). Circumferential strain rate (CSr) decreased at week 6 (-5.5 ± 0.8 to -4.6 ± 1.0 per second, P = 0.008). Radial strain/strain rate (RS/RSr) decreased at week 8 (54.8 ± 9.4 to 43.7 ± 10.6%, P = 0.005 for RS; 8.0 ± 1.1 to 7.0 ± 1.1 per second, P = 0.005 for RSr), while there was no significant change in LS/LSr, LVEF, CS/CSr, or RS/RSr in the control group. LVEF had the highest correlation with LS (r =-0.607, P = 0.000) and the lowest correlation with RSr (r = 0.357, P = 0.000). CONCLUSIONS: In DIC of rat hearts, LS/LSr decreased first, and then LVEF, CS, CSr, RS/RSr subsequently decreased. LS/LSr is considered to be a more sensitive predictor than LVEF in progressive rat DIC, and RS/RSr was preserved until the last stage.

Cardioprotective effects of rosuvastatin and carvedilol on delayed cardiotoxicity of doxorubicin in rats.

CONTEXT: Doxorubicin is widely used anti-neoplastic drug but has serious cardiotoxicity. Long-term cardioprotective effects of statin and carvedilol against delayed cardiotoxicity of doxorubicin was not well elucidated. OBJECTIVE: To evaluate long-term cardioprotective effects of co-administered rosuvastatin and carvedilol against chronic doxorubicin-induced cardiomyopathy (DIC) in rats. METHODS: Sixty-one rats were assigned to six groups: group I, control; group II, doxorubicin only (1.25 mg/kg, bi-daily, I.P.); group III, doxorubicin + rosuvastatin (2 mg/kg/day, P.O.); group IV, doxorubicin + rosuvastatin(10 mg/kg/day, P.O.); group V, doxorubicin + carvedilol (5 mg/kg/day, P.O.); group VI, doxorubicin + carvedilol (10 mg/kg/day, P.O.). Drugs were administered for 4 weeks (by week 4) and rats were observed without drugs for 4 weeks (by week 8). RESULTS: After 4 weeks discontinuation of drugs (week 8), group III showed higher +dP/dt (p = 0.058), lower -dP/dt (p = 0.009), lower left ventricular (LV) tissue malondialdehyde (MDA; p = 0.022), and less LV fibrosis (p = 0.011) than group II. Group IV showed similar results to group III. However, in group V and VI, carvedilol failed to reduce LV dysfunction, elevation of troponin or myocardial fibrosis, although group V showed lower LV tissue MDA (p = 0.004) than group II. DISCUSSION AND CONCLUSIONS: Myocardial injury and LV systolic/diastolic dysfunction at week 8 was alleviated by co-administered rosuvastatin, but not by carvedilol. It is unclear whether the cardioprotective effect of rosuvastatin is attributed to a suppression of oxidative stress induced by doxorubicin, because carvedilol did not exhibit a cardioprotective effect despite its antioxidant effects.

Simultaneous and spontaneous multivessel coronary artery dissection presenting as congestive heart failure.

Spontaneous coronary artery dissection (SCAD) is a rare cause of myocardial ischemia. Multivessel SCAD is much rarer than single vessel involvement and acute coronary syndrome is the most frequent clinical presentation of a patient with SCAD. The patient in this report had SCAD in both the left anterior descending and right coronary arteries at the same time. However, the clinical manifestation was not acute coronary syndrome but rather congestive heart failure. Successful angioplasty and stent placement was performed and the symptoms of congestive heart failure were successfully resolved with medical treatment.

Association between C-reactive protein and QTc interval in middle-aged men and women.

BACKGROUND: Both of prolonged QT interval and elevated C-reactive protein (CRP) levels are known to be risk factors of cardiovascular disease. To our knowledge, few studies have reported the direct relationship between CRP levels and the QT interval in middle-aged population. The objective of the present study was to examine the association of CRP level with QT interval. METHODS AND RESULTS: A total of 2471 men and 2287 women from the Korea n Health and Genome study underwent physical examination and completed a questionnaire. A 12-lead electrocardiogram (ECG) recording was obtained from each subject. Subjects who were taking statins, non-steroidal anti-inflammatory drugs (NSAID) and postmenopausal hormone replacement therapy, which are known to have an effect on CRP levels, were excluded. Geometric means of CRP levels were compared among three groups, which were classified by heart rate-corrected QT (QTc) interval: prolonged (> or =440 msec in men and > or =450 msec in women), borderline (420-439 msec in men and 430-449 msec in women) and normal (<420 msec in men and <430 msec in women) groups. The means of CRP level in women, though over normal range, increased significantly as QTc interval was longer, independent of confounding factors, while those of men were on the borderline of significance. However, compared to normal range of QTc interval, prolonged QTc interval was associated with elevated CRP level, defined as more than 95 percentile of CRP, in men and women, respectively. CONCLUSIONS: Prolonged QTc interval in middle-aged men and women is associated with the elevated CRP, independent of confounding factors.