Two Cases of Reversible Left Ventricular Hypertrophy during Recovery from Takotsubo Cardiomyopathy

We report 2 cases of reversible ventricular hypertrophy in patients with takotsubo cardiomyopathy (stress‐induced cardiomyopathy) during recovery of cardiac function. The first case involved a 72‐year‐old woman who presented with cerebral infarction. On admission, an elevated troponin I and decreased apical wall motion were observed with normal myocardial perfusion imaging. The second case involved a 79‐year‐old woman who presented with angina, anxiety resulting from emotional stress, slightly decreased apical wall motion, and normal epicardial arteries. In both cases, apical hypertrophy of the left ventricle was observed at approximately 3 weeks after onset, when the wall motion had improved. The ventricular wall gradually became thinner over time. To our knowledge, this is the first report of reversible ventricular hypertrophy in patients with takotsubo cardiomyopathy. We hypothesize the hypertrophic signaling in the myocardium was stimulated by catecholamines, which are the suggested etiology of takotsubo cardiomyopathy, and the hypertrophied myocardium gradually returned to normal as the syndrome receded.     

A case of recurrent earthquake stress cardiomyopathy with a differing wall motion abnormality

We present the case of a Caucasian woman who survived two major earthquakes, presenting on each occasion with stress cardiomyopathy, but with a different pattern of regional wall motion abnormality on the second occasion. The first Christchurch earthquake struck on September 4, 2010. At 7.1 on the Richter scale, it was larger than the major Haiti quake, but miraculously there were no direct fatalities. In the week following, eight women meeting modified Mayo criteria for stress cardiomyopathy presented to Christchurch Hospital. The second Christchurch earthquake was on February 22, 2011. It measured 6.4 on the Richter scale and caused 180 direct fatalities. In the week following this earthquake, 24 women were admitted with stress cardiomyopathy. One patient presented after both earthquakes. This 76-year-old woman first presented on September 4 with 10 hours of chest pain. Electrocardiogram showed inferolateral deep T-wave inversion and QT prolongation. TnI peaked at 0.81 μg/L. Coronary angiography demonstrated diffuse atheroma with a moderate mid LAD lesion that was stented at the time. Echocardiography showed a classic takotsubo pattern. Her follow-up echocardiogram on September 28 was normal and she was completely well at that point. However, during the second earthquake of February 22, she again developed chest pain and shortness of breath. TnI peaked at 1.3 μg/L. Echocardiogram showed a midwall variant takotsubo with apical sparing. She was discharged from hospital on the 25th, planning to leave Christchurch for a new home in another city, but returned for follow-up echocardiogram on July 27. This was normal.     

Recurrent Takotsubo Cardiomyopathy Related to Recurrent Thyrotoxicosis

Takotsubo cardiomyopathy, or transient left ventricular apical ballooning syndrome, is characterized by acute left ventricular dysfunction caused by transient wall-motion abnormalities of the left ventricular apex and mid ventricle in the absence of obstructive coronary artery disease. Recurrent episodes are rare but have been reported, and several cases of takotsubo cardiomyopathy have been described in the presence of hyperthyroidism. We report the case of a 55-year-old woman who had recurrent takotsubo cardiomyopathy, documented by repeat coronary angiography and evaluations of left ventricular function, in the presence of recurrent hyperthyroidism related to Graves disease. After both episodes, the patient''s left ventricular function returned to normal when her thyroid function normalized. These findings suggest a possible role of thyroid-hormone excess in the pathophysiology of some patients who have takotsubo cardiomyopathy.     

Evolutionary Change Mimicking Apical Hypertrophic Cardiomyopathy in a Patient with Takotsubo Cardiomyopathy

In this report, we introduce a case of thickening of the involved left ventricular apical segment on echocardiography and deep T‐wave inversions in precordial leads on electrocardiography transiently seen in the course of recovery from biventricular takotsubo cardiomyopathy, mimicking apical hypertrophic cardiomyopathy. This result suggests that the echocardiographic finding of transient myocardial edema can be identified by cardiac magnetic resonance imaging in takotsubo cardiomyopathy. Additionally, it persisted a few weeks after full functional recovery. We believe that this case will contribute in part toward clarifying the pathophysiology of takotsubo cardiomyopathy.     

Recurrent long QT syndrome and syncope in transient apical ballooning syndrome (takotsubo cardiomyopathy)

Transient apical ballooning syndrome, or takotsubo cardiomyopathy is a syndrome characterized by reversible dilation of the left ventricular apex. It usually occurs in response to stress, and resolves completely in a few weeks. The present report describes a 55-year-old woman who presented with chest pain and syncope in response to emotional stress. Her electrocardiogram suggested acute coronary syndrome with prolonged QT. However, cardiac catheterization showed normal coronary arteries, with apical akinesis of the left ventricle. The patient’s symptoms recurred 18 months later; subsequently, she was diagnosed with recurrent takotsubo cardiomyopathy with prolonged QT and syncope. The treatment, etiology and pathophysiology of takotsubo cardiomyopathy are discussed.     

Two Cases of Apical Ballooning Syndrome Masking Apical Hypertrophic Cardiomyopathy

Apical akinesis and dilation in the absence of obstructive coronary artery disease is a typical feature of stress-induced (takotsubo) cardiomyopathy, whereas apical hypertrophy is seen in apical-variant hypertrophic cardiomyopathy. We report the cases of 2 patients who presented with takotsubo cardiomyopathy and were subsequently found to have apical-variant hypertrophic cardiomyopathy, after the apical ballooning from the takotsubo cardiomyopathy had resolved. The first patient, a 43-year-old woman with a history of alcohol abuse, presented with shortness of breath, electrocardiographic and echocardiographic features consistent with takotsubo cardiomyopathy, and no significant coronary artery disease. An echocardiogram 2 weeks later revealed a normal left ventricular ejection fraction and newly apparent apical hypertrophy. The 2nd patient, a 70-year-old woman with pancreatitis, presented with chest pain, apical akinesis, and a left ventricular ejection fraction of 0.39, consistent with takotsubo cardiomyopathy. One month later, her left ventricular ejection fraction was normal; however, hypertrophy of the left ventricular apex was newly noted. To our knowledge, these are the first reported cases in which apical-variant hypertrophic cardiomyopathy was masked by apical ballooning from stress-induced cardiomyopathy.     

Spiral Hypertrophic Cardiomyopathy as Detected by Cardiac Magnetic Resonance

Hypertrophic cardiomyopathy (HCM) is a genetically determined heart muscle disease; characterized by left ventricular hypertrophy. Spiral HCM is described as having a counterclockwise rotation pattern of hypertrophy along with variable degrees of fibrosis. A 34‐year‐old female presented with symptoms suggestive of heart failure. Echocardiography showed concentric left ventricular hypertrophy with normal contractility. Cardiac MRI showed asymmetric septal hypertrophy with mid‐cavity obliteration and a spiral pattern of variably increasing wall thickness. Late gadolinium enhancement demonstrated several areas of abnormal post‐gadolinium uptake. We report a case of spiral HCM. We should consider cardiovascular magnetic resonance as the reference standard for diagnosing HCM.     

Melatonin receptor activation protects against low potassium‐induced ventricular fibrillation by preserving action potentials and connexin‐43 topology in isolated rat hearts

Hypokalemia prolongs the QRS and QT intervals, deteriorates intercellular coupling, and increases the risk for arrhythmia. Melatonin preserves gap junctions and shortens action potential as potential antiarrhythmic mechanisms, but its properties under hypokalemia remain unknown. We hypothesized that melatonin protects against low potassium‐induced arrhythmias through the activation of its receptors, resulting in action potential shortening and connexin‐43 preservation. After stabilization in Krebs‐Henseleit solution (4.5 mEq/L K⁺), isolated hearts from Wistar rats underwent perfusion with low‐potassium (1 mEq/L) solution and melatonin (100 μmol/L), a melatonin receptor blocker (luzindole, 5 μmol/L), melatonin + luzindole or vehicle. The primary endpoint of the study was the prevention of ventricular fibrillation. Electrocardiography was used, and epicardial action potentials and heart function were measured and analyzed. The ventricular expression, dephosphorylation, and distribution of connexin‐43 were examined. Melatonin reduced the incidence of low potassium‐induced ventricular fibrillation from 100% to 59%, delayed the occurrence of ventricular fibrillation and induced a faster recovery of sinus rhythm during potassium restitution. Melatonin prevented QRS widening, action potential activation delay, and the prolongation of action potential duration at 50% of repolarization. Other ECG and action potential parameters, the left ventricular developed pressure, and nonsustained ventricular arrhythmias did not differ among groups. Melatonin prevented connexin‐43 dephosphorylation and its abnormal topology (lateralization). Luzindole abrogated the protective effects of melatonin on electrophysiological properties and connexin‐43 misdistribution. Our results indicate that melatonin receptor activation protects against low potassium‐induced ventricular fibrillation, shortens action potential duration, preserves ventricular electrical activation, and prevents acute changes in connexin‐43 distribution. All of these properties make melatonin a remarkable antifibrillatory agent.     

Heart rate variability and baroreflex sensitivity in idiopathic dilated cardiomyopathy

OBJECTIVE—To examine the relation between cardiac autonomic tone, assessed by baroreflex sensitivity and heart rate variability, and left ventricular function, arrhythmias on Holter monitoring, and clinical variables in patients with idiopathic dilated cardiomyopathy.
DESIGN—A prospective observational study.
PATIENTS—160 patients with idiopathic dilated cardiomyopathy and preserved sinus rhythm in the absence of antiarrhythmic drug treatment. Measures of heart rate variability obtained by digital 24 hour Holter recordings included the mean of all coupling intervals between normal beats (RRm), the standard deviation of the mean of normal RR intervals (SDNN), and the square root of the mean of the squared differences between adjacent normal RR intervals (rMSSD). Baroreflex sensitivity testing was performed using the phenylephrine method.
RESULTS—Mean SDNN (SEM) was 112 (46) ms, and baroreflex sensitivity was 7.5 (5.0) ms/mm Hg. SDNN showed a weak correlation with baroreflex sensitivity (r = 0.19, p < 0.05) and with left ventricular ejection fraction (r = 0.29, p < 0.05). SDNN showed no significant correlation with age (r = −0.07), the presence of non-sustained ventricular tachycardia (r = −0.13), or left ventricular end diastolic diameter (r = −0.07). In addition, baroreflex sensitivity showed no significant correlation with age (r = −0.13), non-sustained ventricular tachycardia (r = −0.08), left ventricular end diastolic diameter (r = 0.09), or ejection fraction (r = 0.14).
CONCLUSIONS—The weak correlation between baroreflex sensitivity and heart rate variability suggests that these two indices explore different aspects of cardiac autonomic control in patients with idiopathic dilated cardiomyopathy. The weak or absent correlation between baroreflex sensitivity, heart rate variability, and other potential non-invasive risk predictors, including left ventricular ejection fraction, left ventricular end diastolic diameter, and non-sustained ventricular tachycardia on Holter monitoring, indicate that these variables may have independent prognostic value in idiopathic dilated cardiomyopathy.


Keywords: cardiomyopathy; baroreflex sensitivity; heart rate variability     

Red cell and platelet‐derived microparticles are increased in G6PD‐deficient subjects

In response to oxidative stress and during apoptosis, cells often shed microparticles (MPs), submicron elements carrying phosphatidylserine and protein antigens. Glucose‐6‐phosphate dehydrogenase (G6PD)‐deficient cells are extremely sensitive to oxidative damage that may lead to the formation of MPs. To determine whether G6PD deficiency alters membrane phospholipid asymmetry and increases MPs production, we determined the concentrations and cellular origins of MPs in G6PD‐deficient individuals using flow cytometry. G6PD‐deficient individuals showed an increase in circulating MPs concentrations as compared with G6PD‐normal individuals [1051/μL (865–2532/μL) vs. 258/μL (235–575/μL), P < 0.01]. MPs concentrations were significantly increased with the severity of G6PD deficiency. Median MPs concentrations from individuals with severe G6PD deficiency, and individuals with moderate G6PD deficiency were 2567/μL (1216–2532/μL) and 984/μL (685–2107/μL), respectively (P < 0.01). Importantly, G6PD enzymatic activity was significantly correlated with MPs concentrations with r² = 0.731. MPs found in G6PD deficiency individuals were largely derived from red blood cells (RBCs) (45%) and platelets (30%). Additionally, Atomic Force Microscopy was used to study the morphology and measures the diameter of MPs found in G6PD‐deficient individuals. The mean (SD) width and height of RMPs were 0. 41 (0.18) and 2.04 (0.14) μm, respectively. Together, these results indicate that MP concentration is significantly correlated with G6PD enzymatic activity and is increased in G6PD‐deficient as compared with G6PD‐normal individuals. Our data also provide an evidence for an alteration in cell membrane associated with a decreased in G6PD activity. However, the significance of MPs in G6PD deficiency needs further clarification.     

Complications of low‐dose,echo‐guided alcohol septal ablation

Background : Alcohol septal ablation (ASA) is a catheter‐based intervention that has been used as an alternative to surgical myectomy in highly symptomatic patients with hypertrophic obstructive cardiomyopathy (HOCM). Methods : This retrospective study was designed to evaluate the incidence of major complications in the mid‐term follow‐up of low‐dose (1–2.5 ml of ethanol), echo‐guided alcohol septal ablation. Results : A total of 101 consecutive patients (56 ± 15 years) with highly symptomatic HOCM were enrolled. At 6 months, there was a significant decrease in resting outflow gradient accompanied by reduction in basal septal diameter and improvement in symptoms (P < 0.01). Two patients (2%) experienced procedural ventricular tachycardias terminated by electrical cardioversion. A total of 87 patients (86%) underwent an uneventful postprocedural hospital stay. The postprocedural complete heart block occurred in 10 patients (10%), and subsequent permanent pacemaker was implanted in four cases (4%). Sustained ventricular arrhythmias requiring electrical cardioversion occurred in four patients (4%) within postprocedural hospital stay. Subsequently, ICD was not implanted in any of these cases. The patients were repeatedly examined by Holter ECG monitoring, and in the mid‐term follow‐up (6–50 months), they stayed asymptomatic and without any ventricular arrhythmias. Conclusion : This study demonstrates the same early incidence of complete heart block requiring permanent pacemaker implantation (4%) and sustained ventricular arrhythmias following low‐dose, echo‐guided ASA. © 2009 Wiley‐Liss, Inc.     

Takotsubo Cardiomyopathy

Background  Takotsubo cardiomyopathy is a novel, yet well-described, reversible cardiomyopathy triggered by profound psychological or physical stress with a female predominance. Objective  This review is designed to increase general clinician awareness about the diagnosis, incidence, pathogenesis, and therapies of this entity. Data Sources  A complete search of multiple electronic databases (Pubmed, EMBASE, Science Citation Index) was carried out to identify all full-text, English-language articles published from 1980 to the present date and relevant to this review. Review Methods  The following search terms were used: takotsubo cardiomyopathy, stress-induced cardiomyopathy, and left ventricular apical ballooning syndrome. Citation lists from identified articles were subsequently reviewed and pertinent articles were further identified. Results  Takotsubo cardiomyopathy is typically characterized by the following: 1) acute onset of ischemic-like chest pain or dyspnea, 2) transient apical and mid-ventricular regional wall-motion abnormality, 3) minor elevation of cardiac biomarkers, 4) dynamic electrocardiographic changes, and 5) the absence of epicardial coronary artery disease. The pathogenesis of the syndrome is unknown but has mostly been associated with acute emotional or physiologic stressors. Dote, Sato, Tateishi, Uchida, Ishihara (J Cardiol. 21(2):203–214, 1991); Desmet, Adriaenssens, Dens (Heart. 89(9):1027–1031, Sep., 2003); Bybee, Kara, Prasad, et al. (Ann Intern Med. 141(11):858–865, Dec 7, 2004); Sharkey, Lesser, Zenovich, et al. (Circulation. 111(4):472–479, Feb 1, 2005) The short and long-term prognosis of these patients is overwhelmingly favorable and often only requires supportive therapy. Conclusion  Whether an emotional or physical event precedes one’s symptoms, it is apparent that takotsubo cardiomyopathy case presentations mimic ST-segment elevation myocardial infarction, and thus is an important entity to be recognized by the medical community.     

Association between plasma retinol levels and the risk of all‐cause mortality in general hypertensive patients: A nested case‐control study

To evaluate the association between plasma retinol levels with all‐cause mortality and investigate the possible effect modifiers in general hypertensive patients with no previous cardiovascular disease (CVD). This case‐control study was nested in the China Stroke Primary Prevention Trial (CSPPT), a randomized, double‐blind, controlled trial conducted in 32 communities in Anhui and Jiangsu provinces in China. The current study included 617 cases of all‐cause mortality and 617 controls matched on age (≤1 year), sex, treatment group, and study site. All‐cause mortality was the main outcome in this analysis, which included death due to any reason. The median follow‐up duration was 4.5 years. Overall, there was a U‐shaped relation of plasma retinol with all‐cause mortality. In the threshold effect analysis, the risk of all‐cause mortality significantly decreased with the increase in plasma retinol (per 10 μg/dL increments: OR, 0.73; 95% CI: 0.61‐0.87) in participants with plasma retinol <58.3 μg/dL and increased with the increase in plasma retinol (per 10 μg/dL increments: OR, 1.08; 95% CI: 1.01‐1.16) in those with plasma retinol ≥58.3 μg/L. In participants with plasma retinol <58.3 μg/dL, a stronger inverse association was observed in those with higher time‐averaged SBP (≥140 vs <140 mm Hg; P‐interaction = .034), or higher vitamin E levels (≥11.5 [quartile 4]; vs <11.5 μg/mL; P‐interaction = .013). The present study demonstrated that there was a U‐shaped relationship of plasma retinol levels with the risk of all‐cause mortality in general hypertensive patients, with a turning point around 58.3 μg/dL.     

Vulnerability to Sympathetic Stress Does Not Persist in Takotsubo Stress Cardiomyopathy

ObjectiveOur objective was to investigate whether dobutamine stress echocardiography (DSE) could induce abnormal cardiac function in takotsubo stress cardiomyopathy (TSC) patients in a stable condition after the acute attack.Methods and ResultsThis was a case-control study and a substudy of the Stockholm Myocardial Infarction With Normal Coronaries (SMINC) study. Twenty-two patients with a previous episode of TSC and 22 sex- and age-matched control subjects were recruited from the SMINC study and investigated with the use of DSE. All TSC patients had a previous normal cardiovascular magnetic resonance investigation. Tissue Doppler imaging–derived time phases of the cardiac cycle were recorded to calculate myocardial performance index (MPI) to assess ventricular function. Compared with control subjects at rest, TSC patients had a slightly but significantly higher left ventricular MPI (LV-MPI; 0.53 vs 0.59; P = .01) and as a trend higher right ventricular MPI (0.38 vs 0.47; P = .08), although during DSE these variables did not differ significantly.ConclusionWe found no difference in standard diastolic parameters between TSC and control subjects, but a significant higher value in LV-MPI in the TSC group at rest. However, no such difference could be demonstrated during DSE between the groups, indicating that vulnerability to sympathetic stimulation does not persist in TSC patients.     

Takotsubo cardiomyopathy complicated by high-grade atrioventricular block: A report of two cases

The present report describes two female patients aged 39 and 57 years who experienced loss of consciousness and chest pain due to high-grade atrioventricular block. Both patients demonstrated noncontraction centred on the cardiac apex and excessive contraction at the cardiac base on cardiac ultrasonography and left ventriculography, but neither of them demonstrated any significant stenotic lesions on coronary angiography. Furthermore, neither patient showed elevated serum biomarkers of cardiac injury or serum viral antibodies. In a repeat left ventriculogram two weeks later, the left ventricular wall motion disorder had improved in both patients. Based on these findings, the patients were diagnosed with takotsubo cardiomyopathy. Because the high-grade atrioventricular conduction disorder did not improve in spite of the improvement of left ventricular wall motion disorder, permanent pacemaker implantation was performed. It is extremely rare for takotsubo cardiomyopathy to be complicated by high-grade atrioventricular block. In the present study, both patients had takotsubo cardiomyopathy complicated by high-grade atrioventricular block and eventually underwent permanent pacemaker implantation.     

Torsade de pointes associated with bradycardia and takotsubo cardiomyopathy

Two cases of torsade de pointes associated with bradycardia and takotsubo cardiomyopathy are reported. In both cases, atrioventricular block preceded the occurrence of takotsubo cardiomyopathy. Bradycardia-induced QT interval prolongation seemed to be amplified by the occurrence of takotsubo cardiomyopathy, resulting in torsade de pointes. Temporary ventricular pacing at a high rate decreased the QT interval and prevented the recurrence of torsade de pointes. Because atrioventricular block recurred or persisted even after the resolution of takotsubo cardiomyopathy, the patients received permanent pacemakers.     

Alcohol use disorders and the heart

Alcohol use is an important preventable and modifiable cause of non‐communicable disease, and has complex effects on the cardiovascular system that vary with dose. Observational and prospective studies have consistently shown a lower risk of cardiovascular and all‐cause mortality in people with low levels of alcohol consumption when compared to abstainers (the ‘J’‐shaped curve). Maximum potential benefit occurs at 0.5 to one standard drinks (7–14 g pure ethanol) per day for women (18% lower all‐cause mortality, 95% confidence interval (CI) = 13–22%) and one to two standard drinks (14–28 g ethanol) per day for men (17% lower all‐cause mortality, 95% CI = 15–19%). However, this evidence is contested, and overall the detrimental effects of alcohol far outweigh the beneficial effects, with the risk of premature mortality increasing steadily after an average consumption of 10 g ethanol/day. Blood pressure (BP) is increased by regular alcohol consumption in a dose‐dependent manner, with a relative risk for hypertension (systolic BP > 140 mm Hg or diastolic > 90 mm Hg) of 1.7 for 50 g ethanol/day and 2.5 at 100 g/day. Important reductions in BP readings can be expected after as little as 1 month of abstinence from alcohol. Heavy alcohol consumption in a binge pattern is associated with the development of acute cardiac arrhythmia, even in people with normal heart function. Atrial fibrillation is the most common arrhythmia associated with chronic high‐volume alcohol intake, and above 14 g alcohol/day the relative risk increases 10% for every extra standard drink (14 g ethanol). Ethanol and its metabolites have toxic effects on cardiac myocytes, and alcoholic cardiomyopathy (ACM) accounts for a third of all cases of non‐ischaemic dilated cardiomyopathy. Screening people drinking alcohol above low‐volume levels and delivering a brief intervention may prevent the development of cardiovascular complications. Although people with established cardiovascular disease show improved outcomes with a reduction to low‐volume alcohol consumption, there is no safe amount of alcohol to drink and patients with ACM should aim for abstinence in order to optimize medical treatment.     

A follow up study of myocardial involvement in patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS)

Objective—To investigate cardiac function in patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) and clarify the clinical features of cardiomyopathy in MELAS.
Patients—11 consecutive patients with MELAS (mean age at initial examination 11.3 years, range 4 to 16 years) were enrolled in the study. Six were followed for more than five years.
Results—On echocardiographic examination, three patients showed increased left ventricular end diastolic posterior wall thickness (LVPWTd), exceeding 140% of the normal value. Four patients, including these three, had an ejection fraction of less than 50%, and two also had increased left ventricular end diastolic volume (LVEDV) exceeding 140% of the normal value (%N). The LVPWTd%N was correlated positively with the LVEDV%N (R = 0.669, p < 0.05) and negatively with the ejection fraction (R = −0.6701, p < 0.05). One patient died of heart failure aged 22 years.
Conclusions—The cardiomyopathy in MELAS is characterised by an abnormally thick left ventricular wall with progressive dilatation and poor left ventricular contraction developing over several years, indicating hypertrophic cardiomyopathy advancing to dilated cardiomyopathy.

Keywords: MELAS;  cardiomyopathy