Serum Apolipoprotein-A2 Levels Are a Strong Predictor of Future Cardiovascular Events in Patients Undergoing Percutaneous Coronary Intervention.

BACKGROUND: Because apolipoprotein-A2 (ApoA2), a key component of high-density lipoprotein cholesterol (HDL-C), lacks clear clinical significance, we investigated its impact on cardiovascular events in patients undergoing percutaneous coronary intervention (PCI).Methods and Results: We examined 638 patients who underwent PCI with a new-generation drug-eluting stent for acute or chronic coronary syndrome and had their apolipoprotein levels measured between 2016 and 2021. The patients were divided into 2 groups based on the median serum ApoA2 values, and the incidence of major adverse cardiovascular events (MACE) was assessed. Of the 638 patients, 563 (88%) received statin treatment, with a median serum LDL-C level of 93 mg/dL. Furthermore, 137 patients (21.5%) experienced MACE, and Kaplan-Meier analysis revealed that the higher ApoA2 group had a significantly lower incidence of MACE than the lower ApoA2 group (30.9% vs. 41.6%). However, the other apolipoproteins, including ApoA1, ApoB, ApoC2, ApoC3, and ApoE, showed no significant differences in MACE. Multivariable Cox hazard analysis indicated that ApoA2 was an independent predictor of MACEs (hazard ratio, 0.666; 95% confidence interval, 0.465-0.954). Furthermore, ApoA2 levels exhibited the strongest inverse association with high-sensitivity C-reactive protein levels (rs=-0.479). CONCLUSIONS: Among all the apolipoproteins, the serum ApoA2 level may be the strongest predictor of future cardiovascular events and prognosis in patients undergoing PCI.

Pd/Pa fluctuation with continuous ATP administration indicates inaccurate FFR measurement caused by insufficient hyperemia.

Continuous intravenous adenosine triphosphate (ATP) administration is the standard method for inducing maximal hyperemia in fractional flow reserve (FFR) measurements. Several cases have demonstrated fluctuations in the ratio of mean distal coronary pressure to mean arterial pressure (Pd/Pa) value during ATP infusion, which raised our suspicions of FFR value inaccuracy. This study aimed to investigate our hypothesis that Pd/Pa fluctuations may indicate inaccurate FFR measurements caused by insufficient hyperemia. We examined 57 consecutive patients with angiographically intermediate coronary lesions who underwent fractional flow reverse (FFR) measurements in our hospital between November 2016 and September 2018. Pd/Pa was measured after continuous ATP administration (150 µg/kg/min) via a peripheral forearm vein for 5 min (FFRA); and we analyzed the FFR value variation in the final 20 s of the 5 min, defining 'Fluctuation' as variation range > 0.03. Then, 2 mg of nicorandil was administered into the coronary artery during continued ATP infusion, and the Pd/Pa was remeasured (FFRA+N). Fluctuations were observed in 23 of 57 patients. The cases demonstrating discrepancies of > 0.05 between FFRA and FFRA+N were observed more frequently in the fluctuation group than in the non-fluctuation group (12/23 vs. 1/34; p < 0.0001). The discrepancy between FFRA and FFRA+N values was smaller in the non-fluctuation group (mean difference ± SD; -0.00026 ± 0.04636 vs. 0.02608 ± 0.1316). Pd/Pa fluctuation with continuous ATP administration could indicate inaccurate FFR measurements caused by incomplete hyperemia. Additional vasodilator administration may achieve further hyperemia when Pd/Pa fluctuations are observed.

Acute coronary syndrome with simultaneous two-vessel occlusion De Winter ST-segment depression or reciprocal change?

We discuss a case of acute coronary syndrome (ACS) with simultaneous two-vessel occlusions in a man in his 20s. The serial electrocardiograms (ECG) showed very early dynamic changes of ST-T configuration resulting from ischemic zone depth or area between anterior wall versus inferior wall. The upsloping ST depression along with tall tentorial T waves in the precordial leads, as shown in the index ECG, raises the possibilities of a de Winter pattern. The retrospective assessment of the index ECG identified prominent T waves and a mild degree of ST-segment elevations in the inferior leads, given the electrocardiographic findings previously recorded at his workplace medical examination obtained at a later date. If the subtle ST-segment elevations in leads II, III, and aVF and the tall T waves were not overlooked in the index ECG, the probability of reciprocal ST-segment depressions in the precordial leads should also be taken into account. We recognize our ECG findings as intriguing ST-T deviation patterns that can change depending on the time sequence and anatomical dominancy of two infarct-related arteries. We finally suggest physicians should bear in mind the possibility of simultaneous multiple vessel occlusions when they encounter ACS patients with hemodynamic instability as in this present case.

Optimal Timing of Serial 18F-Fluoro-2-Deoxyglucose Positron Emission Tomography after Prednisolone Treatment Introduction for Cardiac Sarcoidosis.

Immunosuppressive therapy with prednisolone (PSL) is the first-line treatment for cardiac sarcoidosis (CS), and 18F-fluoro-2-deoxyglucose positron emission tomography (FDG-PET) is used to evaluate its efficacy to guide treatment. However, the appropriate timing of FDG-PET in CS remains unknown. This single-center, retrospective, observational study included 15 consecutive CS patients who underwent 3 serial FDG-PET scans (at baseline, in the early phase [1-2 months after PSL introduction], and in the late phase [≥ 5 months after PSL introduction with a maintenance dose of PSL]). We adhered to the PSL tapering protocol by the Japanese Circulation Society even when early FDG-PET showed positive results (SUVmax ≥ 4.0). No patient died during the 908 (644-1600) days of observation. Negative results in the late phase were observed in 3 of 6 early-positive patients, and 3 of 9 early-negative patients showed positive results in the late phase. Changes in echocardiographic parameters from baseline to the late phase were significantly better in late-negative patients than in late-positive patients (left ventricular end-diastolic diameter: -0.7 (-9.3-[-0.5]) mm versus +3.5 (0.8-7.5) mm, P = 0.039; left ventricular end-systolic diameter: -4.2 (-6.9-[-0.1]) mm versus +5.1 (0.5-7.0) mm, P = 0.015; left ventricular ejection fraction: +4.7% (-1.0-9.0%) versus -1.5% (-11.3-1.5%), P = 0.045) ), although early FDG-PET did not predict those consequent changes. An interval of ≥ 5 months after introducing the PSL with a maintenance dose of PSL is long enough for FDG-PET to reflect consequent left ventricular functions, while an interval of 1-2 months can be too short.

Long-Term Outcomes in Patients with Not-Retrieval Inferior Vena Cava Filter Under Anticoagulation.

Since permanent inferior vena cava (IVC) filters increase deep vein thrombosis (DVT), filter retrieval should be performed as possible. Despite the guideline recommendation, IVC filters are not always retrieved in clinical practice. To date, many patients with not-retrieval IVC filters have been prescribed anticoagulant therapy, but the long-term prognosis, including venous thromboembolism (VTE) and bleeding events, remains unknown. In this study, 195 patients who underwent IVC filter implantation between 2006 and 2017 at 3 institutions in Niigata City have been investigated about their deaths, VTE recurrence, and bleeding events. After peaking 2009, the number of IVC filter implantation gradually decreased. During observational period, there were 158 patients with not-retrieval IVC filters (the overall retrieval rate of 19.0%). The not-retrieval group included significantly older and more patients with cancer compared to the retrieval group. Anticoagulation therapy was continued in 88% of the not-retrieval group. During a mean follow-up of 5.0 years, 6 symptomatic DVT events associated with inadequate control of anticoagulation and 13 bleeding events were observed. A total of 52 patients died and only the presence of cancer was prognostic risk factor. Although long-term anticoagulation therapy may be associated with bleeding events, there were few recurrent VTE under optimal anticoagulation. It is anticipated that even if the IVC filter cannot be retrieved, appropriate anticoagulation is useful for prevention of DVT recurrence despite the risk of bleeding.

Relationship Between Heart Rate at Discharge and Long-Term Outcomes of Surgically Treated Patients With Type A Acute Aortic Dissections.

BACKGROUND: Resting heart rate (HR) at discharge is an important predictor of mortality after acute myocardial infarction. However, in patients with Stanford type A acute aortic dissections (TA-AADs), the relationship between HR and long-term outcomes is unclear. Therefore, this relationship was investigated in the present study.Methods and Results:Surgically treated consecutive patients with TA-AAD (n=721) were retrospectively categorized according to HR quartiles, recorded within 24 h before discharge (<70, 70-77, 78-83, and ≥84 beats/min). The study endpoints included aortic aneurysm-related deaths, sudden deaths, aortic surgeries, and hospitalizations for recurrence of acute aortic dissections. The mean (±SD) patient age was 65.8±13.0 years. During a median observation period of 5.8 years (interquartile range 3.9-8.5 years), 17.2% of patients (n=124) experienced late aortic events. Late aortic surgery was performed in 14.0% of patients. After adjusting for potential confounders, including ß-blocker use, HR at discharge remained an independent predictor of long-term aortic outcomes. Patients with discharge HR ≥84 beats/min had a higher risk (hazard ratio 1.86; 95% confidence interval 1.06-3.25; P=0.029) of long-term aortic events than those with HR <70 beats/min; the cumulative survival rates were similar among the groups (log-rank, P=0.905). CONCLUSIONS: In surgically treated patients with TA-AAD, HR at discharge independently predicted long-term aortic outcomes. Consequently, HR in patients with TA-AAD should be optimized before discharge, particularly if the HR is ≥84 beats/min.

Long-Term Prognosis of Patients Who Underwent Percutaneous Transvenous Mitral Commissurotomy for Mitral Stenosis.

The long-term prognosis for up to 20 years of patients who have undergone percutaneous transvenous mitral commissurotomy (PTMC) for mitral stenosis (MS) is unknown.We examined 77 of 93 patients (83%) with MS and who underwent PTMC from 1989 to 2002 at our institute, as well as the occurrence of either one of the following clinical endpoints until September 1, 2018: all-cause death or repeat intervention for the mitral valve.The mean follow-up duration was 20.5 ± 7.3 years. The mean age was 51 ± 11 years. Overall, the 20-year survival rate was 71% ± 5%; without any intervention, the 20-year survival rate was 40% ± 6%. In patients who achieved good immediate results (i.e., mitral valve area (MVA) of ≥ 1.5 cm2 without mitral regurgitation (MR) of > 2/4 after PTMC), the 20-year survival rate was 80% ± 6%; without any intervention, the 20-year survival rate was 54% ± 7%.In our 20-year observational study, patients who have undergone PTMC for MS had favorable prognosis, especially in those who achieved good immediate results. In those who had poor immediate results, careful follow-up is needed because they might have more clinical event and any intervention for the mitral valve.

The Impending Epidemic of Cardiovascular Diseases in Patients With Cancer in Japan.

Onco-cardiology, a new academic field, aims to improve the quality of life and prognosis of cancer patients and survivors with cardiovascular diseases (CVD). With the aging of the population, an epidemic of cancer with CVD is emerging in developed countries. Cancer and CVD share risk factors, pathophysiology, treatments, and preventive and rehabilitative measures. A multidisciplinary team-based approach is needed to support cancer treatment to maximize its effectiveness and minimize its cardiotoxic potential. Basic and clinical onco-cardiology are already being practiced harmoniously. However, systematization in academia and clinical practice and accumulation of evidence have just started. In this review, we present the epidemiology, common risk factors between cancer and CVD, future epidemic of CVD in patients with cancer, and the necessity for an onco-cardiological approach to managing the burden of CVD in cancer patients and survivors.

Burden of cardiovascular disease in Japanese cancer patients and survivors: a single cancer-center study in Niigata City.

BACKGROUND: Cardiovascular disease (CVD) and cancer are major causes of death in Japan. As most CVDs are chronic and often aggravate, long-term follow-up is necessary. Although some cancer patients and survivors have CVD, its prognostic significance and prevalence are unknown. Therefore, we conducted a retrospective study at our center to determine the prevalence of cancer patients with CVD. METHODS: In 2015, our 10-year (2005-2014) cancer registry was summarized. Comorbidities including left ventricular dysfunction, atrial fibrillation (AF), ischemic heart disease, aortic stenosis, venous thromboembolism (VTE), and elevation of N-terminal prohormone of brain natriuretic peptide (NT-proBNP) were examined. RESULTS: In total, 26,235 de novo cancer patients were registered and 16,130 survived until January 1, 2015. The 5-year survival rate was 64.0% for all cancer patients and 44.2% for cancer patients with CVD. Cox proportional hazards analysis adjusting for age, cancer stage, and body mass index revealed that AF [hazard ratio (HR) 1.219, male; P = 0.038], VTE (HR 1.517, male; P = 0.003 and HR 2.089, female; P < 0.001), and NT-proBNP elevation (HR 1.861, female; P = 0.002) were significantly associated with death. The CVD prevalence among cancer survivors in 2015 was 8.7% vs 3.5% for males vs females. AF was the most common CVD (prevalence: male, 4.0%; female, 1.0%). The prevalence of most CVD in adults increased progressively with age, with male predominance (12.1% for male and 7.5% for female patients in the 80 s age group). CONCLUSIONS: One in 10 elderly cancer survivors has serious CVD. AF, VTE, and heart failure were critical comorbidities. Cardiologists and cancer-care providers should recognize CVD presence and monitor patients closely, providing medications or interventions concurrently with cancer therapy.

Future projection of cancer patients with cardiovascular disease in Japan by the year 2039: a pilot study.

BACKGROUND: The number of cancer patients in Japan is estimated to rise to 3.5 million by 2025. The disease burden may be further complicated by comorbidities caused by cardiovascular disease (CVD). Predicting the number of cancer patients with CVD can help anticipate future resource needs. METHODS: We used statistics derived from the Niigata Cancer Center CVD Study (2015) as well as population estimates from the National Cancer Center's Cancer Registry and Statistics survey of 2017 for convenience. We simply multiplied the projected number of cancer patients through the year 2039 by the CVD prevalence in 2015, with patients classified by sex, age, and cancer type to estimate the number of cancer patients with CVD. RESULTS: The total number of Japanese cancer patients with CVD was 253,000 in 2015 and is predicted to increase rapidly by 30,000 in 2020 and peak at 313,000 in 2030-2034. Men will dominate the CVD population at 2.5-fold the number of women. The growth rate of the population with both cancer and CVD will be greater than that of the cancer-only population (1.23 vs 1.18, P < 0.001), and will comprise notably high proportions of patients with prostatic, breast, and uterine cancers (1.80, 1.57, and 1.66, P < 0.001, respectively). CONCLUSION: Future cancer patients will be older and more likely to have CVD. Although men will continue to dominate this population, the increase in the number of women will be pronounced. Cancer care providers should be trained to recognize CVD and provide any necessary interventions concurrently with cancer therapy.

Correction to: Future projection of cancer patients with cardiovascular disease in Japan by the year 2039: a pilot study.

n the original publication, in a title of Table 2.

Clinical Predictors of Recurrent Ventricular Arrhythmias in Secondary Prevention Implantable Cardioverter Defibrillator Recipients With Coronary Artery Disease　- Lower Left Ventricular Ejection Fraction and Incomplete Revascularization.

BACKGROUND: The implantable cardioverter defibrillator (ICD) is a standard prevention therapy for patients at high risk for sudden cardiac death (SCD) due to life-threatening ventricular arrhythmia (VA), that is, ventricular fibrillation and ventricular tachycardia. However, clinical predictors of recurrent VA in secondary prevention ICD recipients with coronary artery disease (CAD) remain unknown. Methods and Results: We followed up 96 consecutive patients with CAD undergoing ICD implantation for secondary prevention of SCD. Long-term rates and clinical predictors of appropriate ICD therapy (ICD-Tx) for VA were analyzed. Appropriate ICD-Tx occurred in 41 (42.7%) patients during a median follow-up of 2.4 years (interquartile range, 0.9-6.1). These patients had significantly greater left ventricular end-diastolic diameter (62.3±1.3 vs. 54.6±1.1 mm, P<0.001), lower left ventricular ejection fraction (LVEF; 36.3±2.0% vs. 45.7±1.8%, P<0.001), and more incomplete revascularization (ICR; 70.7% vs. 45.5%, P=0.014) than those without appropriate ICD-Tx. Multivariable analysis showed that LVEF (hazards ratio [HR], 0.950; 95% CI: 0.925-0.975; P<0.001) and ICR (HR, 2.293; 95% CI: 1.133-4.637; P=0.021) were significant predictors of appropriate ICD-Tx for VA. CONCLUSIONS: Lower LVEF and ICR were independent predictors of recurrent VA in secondary prevention ICD recipients with CAD.

Dual Antiplatelet Therapy Guided by CYP2C19 Polymorphisms after Implantation of Second-Generation Drug-Eluting Stents for Management of Acute Coronary Syndrome.

Prasugrel, a novel P2Y12 receptor inhibitor, is administered to patients with acute coronary syndrome (ACS) after percutaneous coronary intervention (PCI), but it can increase the risk of bleeding. The Japanese exhibit weaker responses to clopidogrel than other races because of CYP2C19 polymorphisms; thus, it is unclear whether these patients should continue dual antiplatelet therapy (DAPT) using prasugrel or switch to clopidogrel in the chronic phase. Here we evaluated the clinical outcomes of DAPT guided by CYP2C19 polymorphisms after implantation of second-generation drug-eluting stents (DESs) for ACS management. Patients with ACS receiving PCI via DES from November 2011 to March 2015 were divided into two groups: conventional DAPT with clopidogrel (n = 41) and gene-guided DAPT (n = 24). In the gene-guided DAPT group, all patients with ACS were given DAPT using prasugrel as soon as possible; extensive and intermediate metabolizers receiving PCI for the first time were switched to clopidogrel at least 2 weeks after discharge, and intermediate metabolizers with repeated ACS and poor metabolizers continued on DAPT using prasugrel. Notably, gene-guided DAPT significantly reduced major adverse cardiovascular/cerebrovascular events (MACCEs; 22.0% versus 4.2%, hazard ratio [HR]: 0.15, 95% confidence interval [CI]: 0.01-0.81; P = 0.0247). Hemorrhagic complications were observed in 3.1% of patients receiving conventional DAPT and absent in the gene-guided group. Moreover, multivariate analysis showed that gene-guided DAPT significantly decreased MACCE incidence (HR: 0.15, 95% CI: 0.01-0.81; P = 0.033). Collectively, these data suggest that CYP2C19 polymorphism analysis may improve treatment decisions in patients with ACS receiving DES-PCI.

Prognosis of Cancer Patients with Aortic Stenosis Under Optimal Cancer Therapies and Conservative Cardiac Treatments.

Aortic stenosis (AS) is a life-threatening comorbidity of cancer patients. Aortic valve replacement (AVR) should be considered for some cancer patients, but neither the characteristics nor prognosis under conservative therapy is well known.We searched our echocardiography log (years 2005-2014) for cancer patients with AS, and 92 patients (54% female) were included in the study. To compare the survival curves, 470 control patients without AS were selected from our cancer registry.Mean age (± SD) was 77.6 ± 6.7 years for males and 81.6 ± 6.3 years for females. Mean aortic valve area (AVA) was 1.0 ± 0.3 cm2. Stomach, blood, and urinary bladder cancers were the major sites of current cancer. During the 5-year follow-up period, 44 patients with AS (48%) died; 26 (59%) due to cancer progression, 10 (23%) heart failure, and 4 (9%) stroke. Heart-failure death was significantly higher for patients with AS than for control patients (P < 0.001). Kaplan-Meier survival estimates were worse for stage I or II patients with AVA < 0.75 cm2 than for control patients (P = 0.016). Older age, advanced stages, absence of dyslipidemia, recent syncope, and chronic heart failure or AVA < 0.75 cm2 were significantly and independently associated with poor survival.Although the majority of cancer patients with AS died of cancer, a quarter died of heart failure. Careful follow-up is needed because cancer patients at earlier stages with symptomatic AS or AVA < 0.75 cm2 should be considered for AVR.

Coronary Aneurysm after Excimer Laser Catheter Ablation and Plain Balloon Angioplasty for Chronic Total Occlusion in a Patient with Kawasaki Disease.

A 37-year-old man with a history of Kawasaki disease presented with total occlusion of the right coronary artery. The patient underwent percutaneous coronary intervention (PCI) with excimer laser coronary angioplasty (ELCA) and plain balloon angioplasty (POBA). Three months after PCI, a coronary aneurysm with restenosis was detected at the PCI site, and PCI was performed again using a small balloon. The aneurysm healed three months after the second PCI procedure. This is the first report describing the long-term outcome after an aneurysm caused by PCI with ELCA and POBA.