BackgroundWhile exercise-based cardiac rehabilitation has a beneficial effect on heart failure hospitalization and mortality, it is limited by the presence of chronotropic incompetence (CI) in some patients. This study explored the feasibility of using wearable devices to assess impaired chronotropic response in heart failure patients.MethodsForty patients with heart failure (left ventricular ejection fraction, LVEF: 44.6 ± 5.8; age: 54.4 ± 11.7) received ECG Holter and accelerometer to monitor heart rate (HR) and physical activities during symptom-limited treadmill exercise testing, 6-min hall walk (6MHW), and 24-h daily living. CI was defined as maximal HR during peak exercise testing failing to reach 70% of age-predicted maximal HR (APMHR, 220 – age). The correlation between HR and physical activities in Holter-accelerometer recording was analyzed.ResultsOf 40 enrolled patients, 26 were able to perform treadmill exercise testing. Based on exercise test reports, 13 (50%) of 26 patients did not achieve at least 70% of APMHR (CI patients). CI patients achieved a lower % APMHR (62.0 ± 6.3%) than non-CI patients who achieved 72.0 ± 1.2% of APMHR (P < 0.0001). When Holter-accelerometer recording was used to assess chronotropic response, the percent APMHR achieved during 6MHW and physical activities was significantly lower in CI patients than in non-CI patients. CI patients had a significantly shorter 6MHW distance and less physical activity intensity than non-CI patients.ConclusionThe study found impaired chronotropic response in 50% of heart failure patients who took treadmill exercise testing. The wearable Holter-accelerometer recording could help to identify impaired chronotropic response to physical activities in heart failure patients.Trial registrationClinicalTrials.gov ID NCT02358603. Registered 16 May 2014.

BackgroundEfficacy and safety of proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors, alirocumab (ALI) and evolocumab (EVO) have previously been evaluated through controlled clinical trials with selective patient groups. Post-commercially, in patients with heterozygous familial hypercholesterolemia (HeFH) and/or cardiovascular disease (CVD) with suboptimal LDL cholesterol (LDLC) lowering on maximal tolerated cholesterol lowering therapy, we assessed efficacy and safety of ALI and EVO.MethodsPost-commercially, we started 25 patients on ALI 75 mg, 15 on ALI 150 mg, and 32 on EVO 140 mg bi-weekly added to entry LDLC lowering regimen, with follow-up for a median 24 weeks. History, physical exam, demographics, and adverse event data were collected. Changes in LDLC and AHA and NIH calculated 10-year CVD risks were assessed on ALI and EVO.ResultsOf 72 patients, 25 had HeFH only, 25 CVD only, 22 had both, median age was 65 years, 63% females, 38% males, 86% Caucasian, 11% African-Americans, 17% diabetics, 63% on anti-hypertensives, and 7% smokers. At entry, 30 (42%) were on a statin and 42 (58%) could not tolerate any statins.At 24-weeks, median LDLC decreased on ALI 75 mg from 117 to 62 mg/dL (−54%), on ALI 150 mg from 175 to 57 mg/dL (−63%), and on EVO 140 mg from 165 to 69 mg/dL (−63%), p <0.0001 for all. Absolute and percent LDLC reduction did not differ (p >.05) between ALI 150 and EVO 140 mg, but were less on ALI 75 mg vs ALI 150 mg and EVO 140 mg (p <.05).Percent reductions in 10-year CVD risks by AHA and NIH calculators, respectively were ALI 75 mg −22 and −44%, ALI 150 mg −31 and −50%, and EVO 140 mg −29 and −56%, p ≤.002 for all.The three most common adverse events included flu-like myositis 10%, respiratory tract symptoms 8%, and injection site reaction 6%.ConclusionIn patients with HeFH and/or CVD, LDLC was lowered by 63% on EVO and ALI 150 mg, and 54% on ALI 75 mg. Adverse events were minimal and tolerable. ALI and EVO represent paradigm shifts in LDLC lowering. Long term, post-commercial safety and efficacy remain to be determined.

BackgroundEfficacy-safety of proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors, alirocumab (ALI) and evolocumab (EVO), have previously been evaluated through controlled clinical trials with selective patient groups. Post-commercially, in 69 patients with heterozygous familial hypercholesterolemia (HeFH) and/or cardiovascular disease (CVD) with suboptimal LDL cholesterol (LDLC) lowering on maximal tolerated LDLC therapy, we assessed efficacy and safety of ALI and EVO.MethodsPost-commercially, we started 29 patients on ALI 75 mg, 18 on ALI 150 mg, and 22 on EVO 140 mg every 2 weeks added to a maximally tolerated LDLC-lowering regimen. Since LDLC lowering did not differ between ALI 150 and EVO 140 mg, ALI 150-EVO 140 data were pooled (ALI-EVO). Changes in LDLC and AHA and NIH calculated 10-year CVD risks were assessed.ResultsOf the 69 patients, 25 had HeFH, 25 CVD, and 19 had both. At entry, 23 (33%) took statins and 46 (67%) were statin-intolerant. Mean ± SD and median follow-up were 49 ± 13 and 49 weeks on ALI 75 mg, and 37 ± 12 and 33 weeks on ALI-EVO. In the ALI-EVO group (n = 40), median LDLC fell from 165 mg/dl at entry to 70 mg/dl (median − 59%, p < .0001). AHA 10-year calculated CVD risk fell from 10.2 to 5.5% (median − 28%, p < .0001), and by the NIH calculator from 14.2 to 3.6% (median − 78%, p < .0001). In the ALI 75 mg group (n = 29), entry LDLC fell from 115 to 68 mg/dl (median − 39%, p < .0001). AHA 10-year calculated CVD risk fell from 11.5 to 7.3% (median − 20%, p = .004), and NIH 10-year risk from 12.9 to 5.1% (median 67%, p < .0001). Absolute and percent change in LDLC was independent of statin use. There were flu-like symptoms in 14% of patients. Adverse events did not differ (p > 0.05) between ALI 75 mg and ALI-EVO.ConclusionIn patients with HeFH and/or CVD, LDLC decreased from 115 to 68 mg/dl (39%) on ALI 75 mg with mean follow-up of 49 weeks, and from 165 to 70 mg/dl (59%) on ALI-EVO over 37 weeks, p < .0001 for both. Adverse events were minimal and tolerable. ALI and EVO represent paradigm shifts in LDLC lowering.

BackgroundWhile exercise-based cardiac rehabilitation has a beneficial effect on heart failure hospitalization and mortality, it is limited by the presence of chronotropic incompetence (CI) in some patients. This study explored the feasibility of using wearable devices to assess impaired chronotropic response in heart failure patients.MethodsForty patients with heart failure (left ventricular ejection fraction, LVEF: 44.6 ± 5.8; age: 54.4 ± 11.7) received ECG Holter and accelerometer to monitor heart rate (HR) and physical activities during symptom-limited treadmill exercise testing, 6-min hall walk (6MHW), and 24-h daily living. CI was defined as maximal HR during peak exercise testing failing to reach 70% of age-predicted maximal HR (APMHR, 220 – age). The correlation between HR and physical activities in Holter-accelerometer recording was analyzed.ResultsOf 40 enrolled patients, 26 were able to perform treadmill exercise testing. Based on exercise test reports, 13 (50%) of 26 patients did not achieve at least 70% of APMHR (CI patients). CI patients achieved a lower % APMHR (62.0 ± 6.3%) than non-CI patients who achieved 72.0 ± 1.2% of APMHR (P < 0.0001). When Holter-accelerometer recording was used to assess chronotropic response, the percent APMHR achieved during 6MHW and physical activities was significantly lower in CI patients than in non-CI patients. CI patients had a significantly shorter 6MHW distance and less physical activity intensity than non-CI patients.ConclusionThe study found impaired chronotropic response in 50% of heart failure patients who took treadmill exercise testing. The wearable Holter-accelerometer recording could help to identify impaired chronotropic response to physical activities in heart failure patients.Trial registrationClinicalTrials.gov ID NCT02358603. Registered 16 May 2014.

BackgroundLymphatic metastasis contributes to the poor prognosis of laryngeal squamous cell carcinoma (LSCC). This study aimed to investigate the roles of two metastasis suppressor genes, KAI1 and nm23, in lymphangiogenesis and lymph metastasis of LSCC.MethodsA total of 45 LSCC patients were enrolled in this study. The positive expression rates of KAI1 and nm23 protein were detected via immunohistochemistry in 45 LSCC and 22 normal laryngeal mucosa adjacent to LSCC. Micro-lymphatic vessel density (MLVD) was detected via immunohistochemistry with the specific antibody D2-40. Associations between KAI1 and nm23 expression and clinical characteristics of LSCC were then evaluated.ResultsThe positive expression rates of KAI1 and nm23 were significantly lower in LSCC than normal laryngeal mucosa (P < 0.05). Significantly lower positive rates of KAI1 and nm23 were found in LSCC with lymphatic metastasis than those without lymphatic metastasis (P < 0.05), whereas MLVD was negatively correlated with the expression of KAI1 and nm23 (P < 0.05). However, no significant associations were found between KAI1 and nm23 expression and clinical characteristics of LSCC (sex, age, disease position, differentiation, and T-stage).ConclusionsBoth KAI1 and nm23 can inhibit lymphangiogenesis and lymphatic metastasis in LSCC.