Letters to the Editor
disruption in chronic heart failure is the hyperadrenergic state, a condition which resembles that of patients with pheochromocytoma, which currently is a well recognized trigger factor for TS. Cases of reversible heart failure induced by pheochromocytoma have also been described in pre-Takotsubo era. The difference between the hyperadrenergic state in CHF and pheochromocytoma is that the cardiac disease will be cured when the tumor is removed in pheochromocytoma. On the contrary, the hyperadrenergic state continues in CHF as long as the root of heart failure is not eliminated. Currently, several treatment modalities with positive effects are adopted in CHF. The most important one is medical sympathectomy with beta blockers. With this novel hypothesis that chronic cardiac sympathetic disruption (chronic TS) with acute exacerbation may be the pathologic mechanism of acute worsening of decompensated CHF, surgical cardiac sympathetic denervation may be considered as a plausible treatment modality and should probably be added to the treatment armamentarium in refractory progressive CHF or heart failure with life threatening arrhythmias. This treatment modality has been adopted in otherwise lethal ventricular arrhythmias. Left or bilateral sympathetic denervation has been used for treatment of patients with refractory ventricular arrhythmias or electrical storm. Bilateral cardiac sympathetic denervation has been shown to be more effective than the left cardiac sympathetic denervation. The beneficial effects of bilateral cardiac sympathetic denervation extend beyond the acute postsympathetic period, with continued freedom from ICD shocks
421
in 48% of patients and a significant reduction in ICD shocks in 90% of patients [9].
References [1] Madias JE. Is there a link between Takotsubo syndrome and some cases of nonischemic cardiomyopathy? A proposal of an animal model. International journal of cardiology 2014;172:e212–3. [2] Park JH, Kang SJ, Song JK, et al. Left ventricular apical ballooning due to severe physical stress in patients admitted to the medical ICU. Chest 2005;128:296–302. [3] Y-Hassan S. The real-world prevalence of Takotsubo syndrome in patients with STelevation myocardial infarction: Highly underestimated. European journal of internal medicine 2014 Feb 21 http://dx.doi.org/10.1016/j.ejim.2014.01.023. [4] Y-Hassan S, Jernberg T. Bromocriptine-induced coronary spasm caused acute coronary syndrome, which triggered its own clinical twin—Takotsubo syndrome. Cardiology 2011;119:1–6. [5] Thygesen K, Alpert JS, Jaffe AS, et al. Third universal definition of myocardial infarction. European heart journal 2012;33:2551–67. [6] Y-Hassan S. Acute cardiac sympathetic disruption in the pathogenesis of the Takotsubo syndrome: a systematic review of the literature to date. Cardiovasc Revasc Med 2014;15:35–42. [7] Y-Hassan S. Chronic Takotsubo syndrome with acute exacerbations may be the villain in the increase of morbidity and mortality in patients with decompensated chronic heart failure. International journal of cardiology 2014;172:609–10. [8] Braunwald E, Kloner RA. The stunned myocardium: prolonged, postischemic ventricular dysfunction. Circulation 1982;66:1146–9. [9] Vaseghi M, Gima J, Kanaan C, et al. Cardiac sympathetic denervation in patients with refractory ventricular arrhythmias or electrical storm: intermediate and long-term follow-up. Heart Rhythm 2014;11:360–6.
http://dx.doi.org/10.1016/j.ijcard.2014.04.040 0167-5273/© 2014 Elsevier Ireland Ltd. All rights reserved.
Hemodynamic and electrocardiographic effects of açaí berry in healthy volunteers: A randomized controlled trial☆ Ashley M. Gale a, Rajbir Kaur b, William L. Baker a,b,⁎ a b
Department of Pharmacy Practice, University of Connecticut School of Pharmacy, Storrs, CT, USA Department of Pharmacy, Hartford Hospital, Hartford, CT, USA
a r t i c l e
i n f o
Article history: Received 14 March 2014 Accepted 2 April 2014 Available online 15 April 2014 Keywords: Açaí QTc interval Herbal products Hemodynamic Blood pressure Heart rate
Açaí berry (Euterpe oleracea Mart.) is derived from the açaí palm that is indigenous to areas of Central and South America. In vitro and in vivo investigations of healthy volunteers, often utilizing blends of ingredients, have demonstrated that the anthocyanins from açaí contain antioxidant and anti-inflammatory properties [1,2]. Animal studies have also suggested various beneficial endothelial, vascular, and hypocholestero☆ This study was presented as a poster presentation at the American College of Clinical Pharmacy's Annual Meeting on Tuesday, October 16th 2013 in Albuquerque, NM. ⁎ Corresponding author at: University of Connecticut, School of Pharmacy, 69 N. Eagleville Rd, Unit 3092, Storrs, CT 06269-3092, USA. Tel.: +1 860 972 7918. E-mail address: [email protected] (W.L. Baker).
lemic actions of açaí [3,4]. However, little information is available on the impact of açaí on cardiovascular parameters that would be of interest to medical practitioners aiding in product selection for patients. The purpose of this study was to evaluate the hemodynamic and electrocardiographic effects of açaí in a healthy volunteer population. This was a randomized, double-blind, placebo-controlled, crossover study conducted in April 2013. The study was approved by the University of Connecticut Institutional Review Board, and all participants provided written informed consent prior to the study. Healthy individuals at least 18 years of age were evaluated for enrollment. Subjects were excluded if any of the following were present: a family history of premature sudden cardiac death; rhythm other than normal sinus; history of atrial or ventricular arrhythmia; left ventricular hypertrophy; atherosclerosis; blood pressure N140/90 mm Hg at time of screening; heart palpitations; baseline corrected QT (QTc) interval N 440 ms; thyroid disease; diabetes mellitus; any psychiatric or neurological condition or disorder; self-reported illicit drug/alcohol abuse; renal or hepatic dysfunction; pregnant or lactating; concurrent use of medications other than for birth control and/or seasonal allergies (excluding pseudoephedrine); or refusal to provide informed consent. In phase 1, participants received two capsules, each of which contained a 500 mg gel capsule of açaí (Nature's Bounty, Inc., Bohemia, NY) or matching placebo. Following a seven day washout, participants returned for phase 2 of the trial and received the opposing treatment. Electrocardiographic and hemodynamic measurements were collected
422
Letters to the Editor
Table 1 Change from baseline in electrocardiographic & hemodynamic parameters. Placebo
Açaí
Difference
p value
341.1 ± 46.6 5.2 ± 30.6 −11.2 ± 33.2
337.3 ± 46.3 − 9.7 ± 42.4 − 18.7 ± 41.2
− 3.8 ± 41.4 −14.9 ± 39.0 − 7.5 ± 54.0
0.703 0.124 0.563
91.0 ± 12.8 0.8 ± 3.3 0.7 ± 4.0
89.4 ± 10.4 1.9 ± 3.3 1.2 ± 3.4
−1.6 ± 8.2 1.1 ± 5.8 0.5 ± 5.7
0.432 0.409 0.697
PR interval (ms) Baseline 4h 6h
142.6 ± 17.9 1.9 ± 7.1 −2.7 ± 9.8
141.2 ± 21.2 −2.6 ± 7.9 −0.2 ± 9.2
− 1.3 ± 7.0 −4.5 ± 10.5 2.5 ± 12.4
0.428 0.078 0.379
Seated systolic pressure (mm Hg) Baseline 4h 6h
119.8 ± 10.2 2.6 ± 7.6 0.1 ± 9.2
121.1 ± 11.2 − 1.7 ± 6.3 0.4 ± 5.9
1.3 ± 10.8 − 4.3 ± 10.2 0.3 ± 10.2
0.615 0.075 0.906
Seated diastolic pressure (mm Hg) Baseline 4h 6h
73.3 ± 9.7 −0.3 ± 5.6 −0.8 ± 6.9
73.6 ± 9.7 − 1.6 ± 6.5 − 0.8 ± 7.2
0.3 ± 8.5 − 1.3 ± 8.9 0.0 ± 9.7
0.902 0.529 0.982
Seated heart rate (bpm) Baseline 4h 6h
78.0 ± 15.1 − 0.1 ± 7.0 − 2.9 ± 7.2
76.4 ± 13.0 0.5 ± 7.8 − 1.8 ± 8.3
− 1.6 ± 11.3 0.6 ± 9.8 1.1 ± 9.3
0.547 0.788 0.596
Standing systolic pressure (mm Hg) Baseline 4h 6h
122.5 ± 11.5 2.3 ± 7.9 2.2 ± 8.5
125.6 ± 15.0 −0.4 ± 9.2 − 4.6 ± 9.3
3.1 ± 13.1 −2.7 ± 11.5 − 6.8 ± 11.4
0.329 0.314 0.015
Standing diastolic pressure (mm Hg) Baseline 78.1 ± 8.7 4h − 1.2 ± 4.7 6h − 0.2 ± 7.4
75.3 ± 7.5 − 0.1 ± 4.9 2.2 ± 6.4
− 2.8 ± 8.6 1.1 ± 7.0 2.4 ± 10.3
0.180 0.489 0.322
Standing heart rate (bpm) Baseline 4h 6h
85.4 ± 13.9 − 2.9 ± 7.2 − 2.5 ± 12.0
− 0.2 ± 12.9 − 0.9 ± 13.8 0.1 ± 13.8
0.943 0.774 0.987
QTc interval (Fredericia) (ms) Baseline 4h 6h QRS interval (ms) Baseline 4h 6h
85.6 ± 17.1 − 1.6 ± 9.7 −2.6 ± 11.2
Comparison between values for patients receiving açaí versus placebo; bpm = beats per minute, ms = milliseconds.
at baseline prior to ingestion of açaí or placebo, and 1, 2, 4, and 6 h postingestion. The co-primary electrocardiogram (ECG) endpoints were the change in QTc from baseline at 4 and 6 h post-ingestion in the açaí versus placebo groups. We also assessed the differences between groups at baseline, 1 and 2 h post-ingestion. Changes in QT, RR, PR, and QRS intervals were also determined. The co-primary hemodynamic endpoints were the change in seated systolic blood pressure (SBP) from baseline at 4 and 6 h postingestion in the açaí versus placebo groups. We also assessed the differences between groups at baseline, 1, and 2 h post-ingestion. Secondary hemodynamic endpoints included the change in seated diastolic blood pressure (DBP), standing SBP and DBP, as well as heart rate during the 6 h post-ingestion period. Information on any potential adverse events was collected at each visit. Continuous data are presented as mean [±standard deviation (SD)], with dichotomous variables expressed as percentages. Intragroup/ intergroup comparisons were performed using the Wilcoxon signed rank test. A p-value of ≤ 0.05 was considered statistically significant. A power calculation was performed under the assumption that an intergroup difference in SBP of 4 ± 4 mm Hg or QTc interval of 6 ± 3 ms would be expected based on the work of Molnar et al. and Corea et al., respectively [5–7]. Using an α-value of 0.05 and power of 80%,
the necessary sample sizes for QTc and SBP are 10 and 4 patients, respectively. Twenty participants (7 men: 4 white, 3 Asian and 13 women: 11 white, 2 Asian) were randomized, but two participants,1 white male and 1 white female, were lost to follow-up. Eighteen participants (mean age: 22.4 ± 2.50 years; mean height: 65.9 ± 2.97 in.; mean weight: 64.5 ± 9.30 kg) completed the study protocol. None were taking medications other than oral contraceptives or medications for seasonal allergies, and none had comorbid conditions. No significant differences were noted in baseline ECG or blood pressure variables between the açaí and placebo groups. After a single dose, no significant differences in any of the primary or secondary ECG endpoints were seen between groups (Table 1). Similarly, no significant differences in any of the primary or secondary hemodynamic endpoints were seen. The only exception was a significantly lower standing SBP seen at 6 h with açaí vs. placebo (−4.6 ± 9.3 mm Hg vs. 2.2 ± 8.5 mm Hg; p = 0.015). No patients after receiving either açaí or placebo reported any adverse effects throughout the duration of the study. This information can often uncover signals of either benefit or harm and spur additional investigation. These types of studies are particularly important since consumers often consider herbal supplements to be harmless, despite their lack of data. Our results are consistent with the
Letters to the Editor
lone published study of açaí [8]. This open label trial of 10 overweight (BMI: 25–30 kg/m2) but otherwise healthy adults evaluated açaí pulp 100 g twice daily for 1 month. They showed that their proprietary frozen product that contained a puree of açaí significantly lowered fasting blood glucose, from 98.0 ± 10.1 mg/dL to 92.8 ± 10.9 mg/dL (p = 0.018), and fasting plasma insulin levels (p = 0.017). Similarly, total cholesterol was reduced from 159 ± 37 mg/dL to 142 ± 28 mg/dL (p = 0.03). No significant changes in SBP, DBP, or heart rate were seen, although specific data was not presented. These hemodynamic effects are similar to those seen in our study with the exception of the lower standing SBP in the açaí group. However, we used a commercially available product that consumers could purchase at their local drug store. Whether the differences in preparations could yield different effects is unclear. To better characterize the hemodynamic and electrophysiologic properties of açaí, a few recommendations for future study can be made. Incorporating testing of serum polyphenol concentrations during the collection periods would demonstrate extent of absorption and provide the ability to model levels to effects seen. Studies should also enroll patients with comorbidities, such as hypertension, and evaluate multiple doses to characterize any dose–response relationship. In conclusion, a single dose of açaí significantly reduced standing SBP, but had no other appreciable electrocardiographic or hemodynamic effects in healthy volunteers.
423
We would like to thank Robin Bogner, PhD for her assistance with production of the blinded active and placebo products. References [1] Jensen GS, Wu X, Patterson KM, et al. In vitro and in vivo antioxidant and antiinflammatory capacities of an antioxidant-rich fruit and berry juice blend. Results of a pilot and randomized, double-blinded, placebo-controlled, crossover study. J Agric Food Chem 2008;56:8326–33. [2] Mertens-Talcott SU, Rios J, Jilma-Stohlawetz P, et al. Pharmacokinetics of anthocyanins and antioxidant effects after the consumption of anthocyanin-rich açaí juice and pulp (Euterpe oleracea Mart.) in human healthy volunteers. J Agric Food Chem 2008;56:7796–802. [3] de Costa CA, de Oliveira PR, de Bem GF, et al. Euterpe oleracea Mart.-derived polyphenols prevent endothelial dysfunction and vascular structural changes in renovascular hypertensive rats: role of oxidative stress. Arch Pharmacol 2012;385:1199–209. [4] de Souza MO, Souza E, Silva L, et al. The hypocholesterolemic activity of açaí (Euterpe oleracea Mart.) is mediated by the enhanced expression of the ATP-binding cassette, subfamily G transporters 5 and 8 and low-density lipoprotein receptor genes in the rat. Nutr Res 2012;32:976–84. [5] Corea L, Cardoni O, Fogari R, et al. Valsartan, a new angiotensin II antagonist for the treatment of essential hypertension: a comparative study of the efficacy and safety against amlodipine. Clin Pharmacol Ther 1996;60:341–6. [6] Molnar J, Zhang F, Weiss J, Ehlert FA, Rosenthal JE. Diurnal pattern of QT interval: how long is prolonged? J Am Coll Cardiol 1996;27:76–83. [7] Caron MF, Hotsko AL, Robertson S, Mandybur L, Kluger J, White CM. Electrocardiographic and hemodynamic effects of Panax ginseng. Ann Pharmacother 2002;36:758–63. [8] Udani JK, Singh BB, Singh VJ, Barrett ML. Effects of açaí (Euterpe oleracea Mart.) berry preparation on metabolic parameters in a healthy overweight population: a pilot study. Nutr J 2011;10:45.
http://dx.doi.org/10.1016/j.ijcard.2014.04.036 0167-5273/© 2014 Elsevier Ireland Ltd. All rights reserved.
Fatal left-dominant arrhythmogenic cardiomyopathy involving a 25-year old professional football player: Could it have been prevented? Francesco Paolo Busardò a, Riccardo Cappato b, Cristian D'Ovidio c, Paola Frati a, Irene Riezzo d, Vittorio Fineschi a,⁎ a
Department of Anatomical, Histological, Forensic and Orthopaedic Sciences, University of Rome Sapienza, 336 Viale Regina Elena, 00185 Rome, Italy IRCCS Policlinico San Donato, San Donato Milanese, Italy c Institute of Legal Medicine, University of Chieti, Italy d Department of Forensic Pathology, University of Foggia, Italy b
a r t i c l e
i n f o
Article history: Received 15 March 2014 Accepted 2 April 2014 Available online 14 April 2014 Keywords: Left-dominant arrhythmogenic cardiomyopathy Plakoglobin Sudden cardiac death Football player
Left-dominant arrhythmogenic cardiomyopathy (LDAC) has recently been recognized as a new pathological variant of arrhythmogenic right ventricular cardiomyopathy (ARVC). Three different patterns have been identified; the “classic” subtype localized in right ventricle, the “biventricular” form characterized by a simultaneous involvement of both ventricles, and the LDAC characterized by an early predominant left ventricle (LV) involvement [1]. The pathological basis of the latter cardiomyopathy subtype involves a replacement of the heart muscle tissue with fibrous and adipose tissue ⁎ Corresponding author. Tel.: +39 06 49912722; fax: +39 06 4455335. E-mail address: vfi[email protected] (V. Fineschi).
associated with an inflammatory infiltrate caused by myocellular death and often appears like a circumferential band in the external one-third of the myocardium and on the right side of the interventricular septum [1,2]. This pathologic tissue may occasionally precipitate ventricular fibrillation [1,3]. In this manuscript, we report the case of a 25-year-old professional football player who, during a football match in the Italian championship league, fell to the ground 30 min after the beginning of the match and remained prone on the field. Resuscitation maneuvers were initiated immediately by means of a bag valve mask for 6.5 min while still on the ground as well as during subsequent ambulance transportation (approximately 3.5 min) to the nearest emergency department. Notably, the semi-automatic portable defibrillator was not used despite its early availability (35 s from start of resuscitation maneuvers) either on the ground or in the ambulance. Finally, ventricular fibrillation was detected and promptly treated with a defibrillator according to the guidelines of the American Heart Association [4] only upon arrival at the emergency department, but because of the onset of a not responsive asystolic rhythm, 1 h and 15 min after the initial cardiovascular collapse the young athlete was declared dead. A complete post-mortem examination was performed 48 h later. Upon inspection, a normal-size heart (440 g) with macroscopic features compatible with the agonistic activity performed by the player was found. Sections of the heart, obtained according to the “short axis”
disruption in chronic heart failure is the hyperadrenergic state, a condition which resembles that of patients with pheochromocytoma, which currently is a well recognized trigger factor for TS. Cases of reversible heart failure induced by pheochromocytoma have also been described in pre-Takotsubo era. The difference between the hyperadrenergic state in CHF and pheochromocytoma is that the cardiac disease will be cured when the tumor is removed in pheochromocytoma. On the contrary, the hyperadrenergic state continues in CHF as long as the root of heart failure is not eliminated. Currently, several treatment modalities with positive effects are adopted in CHF. The most important one is medical sympathectomy with beta blockers. With this novel hypothesis that chronic cardiac sympathetic disruption (chronic TS) with acute exacerbation may be the pathologic mechanism of acute worsening of decompensated CHF, surgical cardiac sympathetic denervation may be considered as a plausible treatment modality and should probably be added to the treatment armamentarium in refractory progressive CHF or heart failure with life threatening arrhythmias. This treatment modality has been adopted in otherwise lethal ventricular arrhythmias. Left or bilateral sympathetic denervation has been used for treatment of patients with refractory ventricular arrhythmias or electrical storm. Bilateral cardiac sympathetic denervation has been shown to be more effective than the left cardiac sympathetic denervation. The beneficial effects of bilateral cardiac sympathetic denervation extend beyond the acute postsympathetic period, with continued freedom from ICD shocks
421
in 48% of patients and a significant reduction in ICD shocks in 90% of patients [9].
References [1] Madias JE. Is there a link between Takotsubo syndrome and some cases of nonischemic cardiomyopathy? A proposal of an animal model. International journal of cardiology 2014;172:e212–3. [2] Park JH, Kang SJ, Song JK, et al. Left ventricular apical ballooning due to severe physical stress in patients admitted to the medical ICU. Chest 2005;128:296–302. [3] Y-Hassan S. The real-world prevalence of Takotsubo syndrome in patients with STelevation myocardial infarction: Highly underestimated. European journal of internal medicine 2014 Feb 21 http://dx.doi.org/10.1016/j.ejim.2014.01.023. [4] Y-Hassan S, Jernberg T. Bromocriptine-induced coronary spasm caused acute coronary syndrome, which triggered its own clinical twin—Takotsubo syndrome. Cardiology 2011;119:1–6. [5] Thygesen K, Alpert JS, Jaffe AS, et al. Third universal definition of myocardial infarction. European heart journal 2012;33:2551–67. [6] Y-Hassan S. Acute cardiac sympathetic disruption in the pathogenesis of the Takotsubo syndrome: a systematic review of the literature to date. Cardiovasc Revasc Med 2014;15:35–42. [7] Y-Hassan S. Chronic Takotsubo syndrome with acute exacerbations may be the villain in the increase of morbidity and mortality in patients with decompensated chronic heart failure. International journal of cardiology 2014;172:609–10. [8] Braunwald E, Kloner RA. The stunned myocardium: prolonged, postischemic ventricular dysfunction. Circulation 1982;66:1146–9. [9] Vaseghi M, Gima J, Kanaan C, et al. Cardiac sympathetic denervation in patients with refractory ventricular arrhythmias or electrical storm: intermediate and long-term follow-up. Heart Rhythm 2014;11:360–6.
http://dx.doi.org/10.1016/j.ijcard.2014.04.040 0167-5273/© 2014 Elsevier Ireland Ltd. All rights reserved.
Hemodynamic and electrocardiographic effects of açaí berry in healthy volunteers: A randomized controlled trial☆ Ashley M. Gale a, Rajbir Kaur b, William L. Baker a,b,⁎ a b
Department of Pharmacy Practice, University of Connecticut School of Pharmacy, Storrs, CT, USA Department of Pharmacy, Hartford Hospital, Hartford, CT, USA
a r t i c l e
i n f o
Article history: Received 14 March 2014 Accepted 2 April 2014 Available online 15 April 2014 Keywords: Açaí QTc interval Herbal products Hemodynamic Blood pressure Heart rate
Açaí berry (Euterpe oleracea Mart.) is derived from the açaí palm that is indigenous to areas of Central and South America. In vitro and in vivo investigations of healthy volunteers, often utilizing blends of ingredients, have demonstrated that the anthocyanins from açaí contain antioxidant and anti-inflammatory properties [1,2]. Animal studies have also suggested various beneficial endothelial, vascular, and hypocholestero☆ This study was presented as a poster presentation at the American College of Clinical Pharmacy's Annual Meeting on Tuesday, October 16th 2013 in Albuquerque, NM. ⁎ Corresponding author at: University of Connecticut, School of Pharmacy, 69 N. Eagleville Rd, Unit 3092, Storrs, CT 06269-3092, USA. Tel.: +1 860 972 7918. E-mail address: [email protected] (W.L. Baker).
lemic actions of açaí [3,4]. However, little information is available on the impact of açaí on cardiovascular parameters that would be of interest to medical practitioners aiding in product selection for patients. The purpose of this study was to evaluate the hemodynamic and electrocardiographic effects of açaí in a healthy volunteer population. This was a randomized, double-blind, placebo-controlled, crossover study conducted in April 2013. The study was approved by the University of Connecticut Institutional Review Board, and all participants provided written informed consent prior to the study. Healthy individuals at least 18 years of age were evaluated for enrollment. Subjects were excluded if any of the following were present: a family history of premature sudden cardiac death; rhythm other than normal sinus; history of atrial or ventricular arrhythmia; left ventricular hypertrophy; atherosclerosis; blood pressure N140/90 mm Hg at time of screening; heart palpitations; baseline corrected QT (QTc) interval N 440 ms; thyroid disease; diabetes mellitus; any psychiatric or neurological condition or disorder; self-reported illicit drug/alcohol abuse; renal or hepatic dysfunction; pregnant or lactating; concurrent use of medications other than for birth control and/or seasonal allergies (excluding pseudoephedrine); or refusal to provide informed consent. In phase 1, participants received two capsules, each of which contained a 500 mg gel capsule of açaí (Nature's Bounty, Inc., Bohemia, NY) or matching placebo. Following a seven day washout, participants returned for phase 2 of the trial and received the opposing treatment. Electrocardiographic and hemodynamic measurements were collected
422
Letters to the Editor
Table 1 Change from baseline in electrocardiographic & hemodynamic parameters. Placebo
Açaí
Difference
p value
341.1 ± 46.6 5.2 ± 30.6 −11.2 ± 33.2
337.3 ± 46.3 − 9.7 ± 42.4 − 18.7 ± 41.2
− 3.8 ± 41.4 −14.9 ± 39.0 − 7.5 ± 54.0
0.703 0.124 0.563
91.0 ± 12.8 0.8 ± 3.3 0.7 ± 4.0
89.4 ± 10.4 1.9 ± 3.3 1.2 ± 3.4
−1.6 ± 8.2 1.1 ± 5.8 0.5 ± 5.7
0.432 0.409 0.697
PR interval (ms) Baseline 4h 6h
142.6 ± 17.9 1.9 ± 7.1 −2.7 ± 9.8
141.2 ± 21.2 −2.6 ± 7.9 −0.2 ± 9.2
− 1.3 ± 7.0 −4.5 ± 10.5 2.5 ± 12.4
0.428 0.078 0.379
Seated systolic pressure (mm Hg) Baseline 4h 6h
119.8 ± 10.2 2.6 ± 7.6 0.1 ± 9.2
121.1 ± 11.2 − 1.7 ± 6.3 0.4 ± 5.9
1.3 ± 10.8 − 4.3 ± 10.2 0.3 ± 10.2
0.615 0.075 0.906
Seated diastolic pressure (mm Hg) Baseline 4h 6h
73.3 ± 9.7 −0.3 ± 5.6 −0.8 ± 6.9
73.6 ± 9.7 − 1.6 ± 6.5 − 0.8 ± 7.2
0.3 ± 8.5 − 1.3 ± 8.9 0.0 ± 9.7
0.902 0.529 0.982
Seated heart rate (bpm) Baseline 4h 6h
78.0 ± 15.1 − 0.1 ± 7.0 − 2.9 ± 7.2
76.4 ± 13.0 0.5 ± 7.8 − 1.8 ± 8.3
− 1.6 ± 11.3 0.6 ± 9.8 1.1 ± 9.3
0.547 0.788 0.596
Standing systolic pressure (mm Hg) Baseline 4h 6h
122.5 ± 11.5 2.3 ± 7.9 2.2 ± 8.5
125.6 ± 15.0 −0.4 ± 9.2 − 4.6 ± 9.3
3.1 ± 13.1 −2.7 ± 11.5 − 6.8 ± 11.4
0.329 0.314 0.015
Standing diastolic pressure (mm Hg) Baseline 78.1 ± 8.7 4h − 1.2 ± 4.7 6h − 0.2 ± 7.4
75.3 ± 7.5 − 0.1 ± 4.9 2.2 ± 6.4
− 2.8 ± 8.6 1.1 ± 7.0 2.4 ± 10.3
0.180 0.489 0.322
Standing heart rate (bpm) Baseline 4h 6h
85.4 ± 13.9 − 2.9 ± 7.2 − 2.5 ± 12.0
− 0.2 ± 12.9 − 0.9 ± 13.8 0.1 ± 13.8
0.943 0.774 0.987
QTc interval (Fredericia) (ms) Baseline 4h 6h QRS interval (ms) Baseline 4h 6h
85.6 ± 17.1 − 1.6 ± 9.7 −2.6 ± 11.2
Comparison between values for patients receiving açaí versus placebo; bpm = beats per minute, ms = milliseconds.
at baseline prior to ingestion of açaí or placebo, and 1, 2, 4, and 6 h postingestion. The co-primary electrocardiogram (ECG) endpoints were the change in QTc from baseline at 4 and 6 h post-ingestion in the açaí versus placebo groups. We also assessed the differences between groups at baseline, 1 and 2 h post-ingestion. Changes in QT, RR, PR, and QRS intervals were also determined. The co-primary hemodynamic endpoints were the change in seated systolic blood pressure (SBP) from baseline at 4 and 6 h postingestion in the açaí versus placebo groups. We also assessed the differences between groups at baseline, 1, and 2 h post-ingestion. Secondary hemodynamic endpoints included the change in seated diastolic blood pressure (DBP), standing SBP and DBP, as well as heart rate during the 6 h post-ingestion period. Information on any potential adverse events was collected at each visit. Continuous data are presented as mean [±standard deviation (SD)], with dichotomous variables expressed as percentages. Intragroup/ intergroup comparisons were performed using the Wilcoxon signed rank test. A p-value of ≤ 0.05 was considered statistically significant. A power calculation was performed under the assumption that an intergroup difference in SBP of 4 ± 4 mm Hg or QTc interval of 6 ± 3 ms would be expected based on the work of Molnar et al. and Corea et al., respectively [5–7]. Using an α-value of 0.05 and power of 80%,
the necessary sample sizes for QTc and SBP are 10 and 4 patients, respectively. Twenty participants (7 men: 4 white, 3 Asian and 13 women: 11 white, 2 Asian) were randomized, but two participants,1 white male and 1 white female, were lost to follow-up. Eighteen participants (mean age: 22.4 ± 2.50 years; mean height: 65.9 ± 2.97 in.; mean weight: 64.5 ± 9.30 kg) completed the study protocol. None were taking medications other than oral contraceptives or medications for seasonal allergies, and none had comorbid conditions. No significant differences were noted in baseline ECG or blood pressure variables between the açaí and placebo groups. After a single dose, no significant differences in any of the primary or secondary ECG endpoints were seen between groups (Table 1). Similarly, no significant differences in any of the primary or secondary hemodynamic endpoints were seen. The only exception was a significantly lower standing SBP seen at 6 h with açaí vs. placebo (−4.6 ± 9.3 mm Hg vs. 2.2 ± 8.5 mm Hg; p = 0.015). No patients after receiving either açaí or placebo reported any adverse effects throughout the duration of the study. This information can often uncover signals of either benefit or harm and spur additional investigation. These types of studies are particularly important since consumers often consider herbal supplements to be harmless, despite their lack of data. Our results are consistent with the
Letters to the Editor
lone published study of açaí [8]. This open label trial of 10 overweight (BMI: 25–30 kg/m2) but otherwise healthy adults evaluated açaí pulp 100 g twice daily for 1 month. They showed that their proprietary frozen product that contained a puree of açaí significantly lowered fasting blood glucose, from 98.0 ± 10.1 mg/dL to 92.8 ± 10.9 mg/dL (p = 0.018), and fasting plasma insulin levels (p = 0.017). Similarly, total cholesterol was reduced from 159 ± 37 mg/dL to 142 ± 28 mg/dL (p = 0.03). No significant changes in SBP, DBP, or heart rate were seen, although specific data was not presented. These hemodynamic effects are similar to those seen in our study with the exception of the lower standing SBP in the açaí group. However, we used a commercially available product that consumers could purchase at their local drug store. Whether the differences in preparations could yield different effects is unclear. To better characterize the hemodynamic and electrophysiologic properties of açaí, a few recommendations for future study can be made. Incorporating testing of serum polyphenol concentrations during the collection periods would demonstrate extent of absorption and provide the ability to model levels to effects seen. Studies should also enroll patients with comorbidities, such as hypertension, and evaluate multiple doses to characterize any dose–response relationship. In conclusion, a single dose of açaí significantly reduced standing SBP, but had no other appreciable electrocardiographic or hemodynamic effects in healthy volunteers.
423
We would like to thank Robin Bogner, PhD for her assistance with production of the blinded active and placebo products. References [1] Jensen GS, Wu X, Patterson KM, et al. In vitro and in vivo antioxidant and antiinflammatory capacities of an antioxidant-rich fruit and berry juice blend. Results of a pilot and randomized, double-blinded, placebo-controlled, crossover study. J Agric Food Chem 2008;56:8326–33. [2] Mertens-Talcott SU, Rios J, Jilma-Stohlawetz P, et al. Pharmacokinetics of anthocyanins and antioxidant effects after the consumption of anthocyanin-rich açaí juice and pulp (Euterpe oleracea Mart.) in human healthy volunteers. J Agric Food Chem 2008;56:7796–802. [3] de Costa CA, de Oliveira PR, de Bem GF, et al. Euterpe oleracea Mart.-derived polyphenols prevent endothelial dysfunction and vascular structural changes in renovascular hypertensive rats: role of oxidative stress. Arch Pharmacol 2012;385:1199–209. [4] de Souza MO, Souza E, Silva L, et al. The hypocholesterolemic activity of açaí (Euterpe oleracea Mart.) is mediated by the enhanced expression of the ATP-binding cassette, subfamily G transporters 5 and 8 and low-density lipoprotein receptor genes in the rat. Nutr Res 2012;32:976–84. [5] Corea L, Cardoni O, Fogari R, et al. Valsartan, a new angiotensin II antagonist for the treatment of essential hypertension: a comparative study of the efficacy and safety against amlodipine. Clin Pharmacol Ther 1996;60:341–6. [6] Molnar J, Zhang F, Weiss J, Ehlert FA, Rosenthal JE. Diurnal pattern of QT interval: how long is prolonged? J Am Coll Cardiol 1996;27:76–83. [7] Caron MF, Hotsko AL, Robertson S, Mandybur L, Kluger J, White CM. Electrocardiographic and hemodynamic effects of Panax ginseng. Ann Pharmacother 2002;36:758–63. [8] Udani JK, Singh BB, Singh VJ, Barrett ML. Effects of açaí (Euterpe oleracea Mart.) berry preparation on metabolic parameters in a healthy overweight population: a pilot study. Nutr J 2011;10:45.
http://dx.doi.org/10.1016/j.ijcard.2014.04.036 0167-5273/© 2014 Elsevier Ireland Ltd. All rights reserved.
Fatal left-dominant arrhythmogenic cardiomyopathy involving a 25-year old professional football player: Could it have been prevented? Francesco Paolo Busardò a, Riccardo Cappato b, Cristian D'Ovidio c, Paola Frati a, Irene Riezzo d, Vittorio Fineschi a,⁎ a
Department of Anatomical, Histological, Forensic and Orthopaedic Sciences, University of Rome Sapienza, 336 Viale Regina Elena, 00185 Rome, Italy IRCCS Policlinico San Donato, San Donato Milanese, Italy c Institute of Legal Medicine, University of Chieti, Italy d Department of Forensic Pathology, University of Foggia, Italy b
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Article history: Received 15 March 2014 Accepted 2 April 2014 Available online 14 April 2014 Keywords: Left-dominant arrhythmogenic cardiomyopathy Plakoglobin Sudden cardiac death Football player
Left-dominant arrhythmogenic cardiomyopathy (LDAC) has recently been recognized as a new pathological variant of arrhythmogenic right ventricular cardiomyopathy (ARVC). Three different patterns have been identified; the “classic” subtype localized in right ventricle, the “biventricular” form characterized by a simultaneous involvement of both ventricles, and the LDAC characterized by an early predominant left ventricle (LV) involvement [1]. The pathological basis of the latter cardiomyopathy subtype involves a replacement of the heart muscle tissue with fibrous and adipose tissue ⁎ Corresponding author. Tel.: +39 06 49912722; fax: +39 06 4455335. E-mail address: vfi[email protected] (V. Fineschi).
associated with an inflammatory infiltrate caused by myocellular death and often appears like a circumferential band in the external one-third of the myocardium and on the right side of the interventricular septum [1,2]. This pathologic tissue may occasionally precipitate ventricular fibrillation [1,3]. In this manuscript, we report the case of a 25-year-old professional football player who, during a football match in the Italian championship league, fell to the ground 30 min after the beginning of the match and remained prone on the field. Resuscitation maneuvers were initiated immediately by means of a bag valve mask for 6.5 min while still on the ground as well as during subsequent ambulance transportation (approximately 3.5 min) to the nearest emergency department. Notably, the semi-automatic portable defibrillator was not used despite its early availability (35 s from start of resuscitation maneuvers) either on the ground or in the ambulance. Finally, ventricular fibrillation was detected and promptly treated with a defibrillator according to the guidelines of the American Heart Association [4] only upon arrival at the emergency department, but because of the onset of a not responsive asystolic rhythm, 1 h and 15 min after the initial cardiovascular collapse the young athlete was declared dead. A complete post-mortem examination was performed 48 h later. Upon inspection, a normal-size heart (440 g) with macroscopic features compatible with the agonistic activity performed by the player was found. Sections of the heart, obtained according to the “short axis”
