Repolarization Changes Research Articles

The Impact of 3:1 Ketogenic Diet on Cardiac Repolarization Changes in Children with Refractory Seizures: A Prospective Follow-Up Study.

Background The association between ketogenic diet (KD) and prolonged QT interval, life-threatening ventricular arrhythmias, and sudden death is controversial. Aim We aimed to prospectively evaluate the effect of KD on electrocardiography (ECG) measures in children with refractory epilepsy. Method A total of 70 children with drug-resistant epilepsy who received a KD for at least 12 months were included in the study. The standard 12-lead electrocardiography was performed in all patients before the beginning and in the 12th month of KD. Heart rate, P-wave duration and dispersion, corrected QT interval and QT dispersion, and Tp-e interval were measured. Results All ECG-derived parameters, but P-wave dispersion increased after 12 months of KD compared with the baseline values. However, these changes were not statistically significant. Conclusion A 12-month long 3:1 KD treatment exerts no deleterious effect on cardiac repolarization measures.

NOVEL CLINICAL MANIFESTATION OF VARIANT SCN5A GENE

Brugada syndrome, an autosomal dominant disease caused by loss of function mutation of sodium channel gene (SCN5A). It is classically described as typical repolarization changes on resting electrocardiogram (EKG) and poses an increased risk of sudden cardiac death (SCD) especially during sleep and

NSTEMI of Infero-Posterior wall with WPW ECG Pattern- Importance of St-Segment Depression In Anterior Leads-A Case Report

Wolff-Parkinson-White Syndrome is a type of pre-excitation syndrome and Inferior lead pseudo-infarct Q waves are a common finding in the Wolff-Parkinson-White (WPW) syndrome. Pseudo-infarct Q waves in the inferior leads are associated with positive or isoelectric T waves in a large number of patients. This characteristic Q wave-T wave vector discordance results from secondary repolarisation changes due to altered ventricular activation. As a corollary, the presence of T wave inversion with inferior lead Q waves and a short PR interval is strongly suggestive, but not pathognomonic of inferior ischemia. The Authors describe an interesting case of Non ST-Elevation Myocardial Infarction involving the inferoposterior wall needing percutaneous coronary intervention of a tight proximal to mid Right coronary artery lesion in a patient whose ECG showed WPW pattern with significant ST-Segment depression in anterior leads V1 to V5 . Significant ST-Segment depression in anterior chest leads with WPW pattern should not be ignored as secondary or discordant ST-T change. Otherwise, Acute Myocardial Infarction may be missed. Key words : Wolff-Parkinson-White Syndrome, Non ST–Elevation Myocardial Infarction(NSTEMI), Pseudo-infarct pattern, ST-segment depression, Discordant ST-T segment.

Gender peculiarities of cardiac performance in children with bronchial asthma.

By the data of clinical-instrumental examination there was performed comparative assessment of gender differences in cardiac performance of 54 patients aged 5 -15 years with persisting form of partially controlled atopic bronchial asthma in inter-attack period of disease. Children were divided in two groups depending on gender - 28 boys and 26 girls . Group of comparison included 52 healthy children - 26 girls and 26 boys . In the girls in the inter - attack period of asthma reliably more often than in the boys there were revealed ventilation disturbance in the lungs by obstructive type ; this promoted rise of pressure in the pulmonary artery. Herewith only in girls in 15,4% of cases there was revealed arterial pulmonary hypertension of a mild form. By the data of echocardiography in girls with bronchial asthma as compared with boys more expressed dilatation both of the right and left ventricles of the heart was observed. Average means of left ventricle contractility both in girls and boys in the inter-attack period of bronchial asthma were reliably decreased (р<0,01) as compared with healthy children, but in girl-patients as compared with boys these deviations were more significant. In the majority of such cases ( in girls – 73,9%, in boys – 53,8%) decrease of contractile myocardium function was caused by presence of metabolic disorders in the form of repolarization changes of ventricular complex ob electrocardiogram. Investigations performed showed presence of some gender differences in cardiac performance in bronchial asthma children which should be considered in the course of treatment.

Remote ischaemic preconditioning shortens QT intervals during exercise in healthy subjects

The protective action of remote ischaemic preconditioning (RIPC) has been demonstrated in the context of surgical interventions in cardiology. Application of RIPC to sports performance has been proposed, but its effect on the electrocardiogram (ECG) during exercise remains unknown. This exploratory study aims to measure the changes in ventricular repolarization observed during exercise following RIPC in healthy subjects. In an experimental randomized crossover study, 17 subjects underwent two bouts of constant load exercise tests at 75% and 115% of gas exchange threshold (GET). Prior to exercise, they were allocated to either control or RIPC intervention with four cycles of 5 min of ischaemia followed by 5 min of reperfusion. ECG was continuously recorded during the protocol. QT and RR intervals were measured every 30 s (on an average tracing of the preceding 10 s). Although the time course of RR intervals did not differ between the two interventions (p = .56 at 75% GET and p = .74 at 115% GET), a significant shortening of QT intervals (measured from Q onset to T end) was observed during exercise (mean ± standard deviation of RIPC vs. control: −32 ± 19 ms at 75% GET (p < .001) and −34 ± 12 ms at 115% GET (p < .001)) as well as during recovery (−21 ± 8 ms at 75% GET (p < .001) and −16 ± 11 ms at 115% GET (p < .001)). This effect was not present at rest. These RIPC-related changes were clearly identifiable on the QT–RR loops after hysteresis reduction. RIPC therefore induces heart rate-independent shortening of QT intervals that is revealed during exercise.

Electrocardiographic patterns of Mangalarga Marchador horses before and after implementation of the marcha gait

ABSTRACT: The aim of this study was to evaluate the electrocardiographic parameters in Mangalarga Marchador horses submitted to marcha exercise. Twenty-four Mangalarga Marchador horses, thirteen females and eleven males, 6.4±2.7 years old with a mean weight of 428.3±24.7kg, were used. Electrocardiograms were recorded in two different moments: rest and immediately after exercise (40 minutes of aerobic exercise, marcha gait). The electrocardiographic variables analyzed were cardiac rhythm, heart rate (HR), duration of P wave, QRS complex, PR and QT intervals, amplitudes of P, R and T waves, and analysis of QT corrected (QTc) according to Bazett's formula (QT/√RR). Variables were analyzed for normality with Kolmogorov-Smirnov test and paired t-test, considering P&lt;0.05. Rhythm analysis revealed 91.7% of sinus rhythm and 8.3% of sinus arrhythmia in rest, with mean HR of 45.7±12.7 beats minute-1, and 100% of sinus tachycardia, with mean HR of 77.3±13.5 beats minute-1 after exercise (P&lt;0.0001). In post-exercise, it was possible to observe decreases in P wave duration (P=0.0121), PR interval (P=0.0007) and QT interval (P&lt;0.0001) and increase of QTc (P=0.0039) and R wave amplitude (P=0.0033). There were no significant differences for amplitude of P and T waves and QRS complex related to atrioventricular enlargement. Although QT interval decreased after exercise, there was an increase on QTc after exercise, indicating changes in ventricular repolarization. It was possible to conclude that the imposed exercise (marcha gait) led to electrocardiographic alterations without causing pathological arrhythmias.

Major rapid weight loss induces changes in cardiac repolarization

IntroductionObesity is associated with increased all-cause mortality, but weight loss may not decrease cardiovascular events. In fact, very low calorie diets have been linked to arrhythmias and sudden death. The QT interval is the standard marker for cardiac repolarization, but T-wave morphology analysis has been suggested as a more sensitive method to identify changes in cardiac repolarization. We examined the effect of a major and rapid weight loss on T-wave morphology. Methods and ResultsTwenty-six individuals had electrocardiograms (ECG) taken before and after eight weeks of weight loss intervention along with plasma measurements of fasting glucose, HbA1c, and potassium. For assessment of cardiac repolarization changes, T-wave Morphology Combination Score (MCS) and ECG intervals: RR, PR, QT, QTcF (Fridericia-corrected QT-interval), and QRS duration were derived.The participants lost on average 13.4% of their bodyweight. MCS, QRS, and RR intervals increased at week 8 (p<0.01), while QTcF and PR intervals were unaffected. Fasting plasma glucose (p<0.001) and HbA1c both decreased at week 8 (p<10−5), while plasma potassium was unchanged. MCS but not QTcF was negatively correlated with HbA1c (p<0.001) and fasting plasma glucose (p<0.01). ConclusionRapid weight loss induces changes in cardiac repolarization. Monitoring of MCS during calorie restriction makes it possible to detect repolarization changes with higher discriminative power than the QT-interval during major rapid weight loss interventions. MCS was correlated with decreased HbA1c. Thus, sustained low blood glucose levels may contribute to repolarization changes.

Syncope and Early Repolarization: A Benign or Dangerous ECG Finding?

Early repolarization is a well-described, common electrocardiographic variant. It was initially felt to be benign, but in the last twenty years a suggested a link between specific types of early repolarization and sudden cardiac death has emerged. This association was has been termed the J wave syndrome and includes both the high risk early repolarization and Brugada ECG patterns. The odds of early repolarization change being associated with poor outcomes are still exceedingly small. Nevertheless, the association of a fairly ubiquitous ECG finding with fatal or near fatal clinical outcomes has raised concern. How can we identify the truly high-risk patients? If a patient has a significant clinical event with a concerning ECG repolarization pattern, what should be done next? The authors of this review present current information regarding the Early Repolarization and Brugada Syndromes and how to proceed with diagnosis, management, and risk stratification when early repolarization change is observed on ECG.

Impact of obstructive and central apneas on ventricular repolarisation: lessons learned from studies in man and pigs.

Sleep apnea (SA) is associated with sudden cardiac death. Compared to central apneas, obstructive apneas are associated with negative intrathoracic pressure swings inducing autonomic imbalance, which may disturb ventricular repolarisation resulting in arrhythmias. To identify the influence of obstructive apneas versus central apneas on ventricular repolarisation. In 14 patients with SA, duration (RT-intervals) and dispersion of ventricular repolarisation [Tpeak-to-Tend-interval (TpTe)] were determined during central apneas compared to obstructive apneas. To identify mechanisms, hypoxia alone or hypoxia with applied negative thoracic pressure was applied in a pig model for SA before and after atropine (n=7), atenolol (n=5) and sympathetic renal denervation (RDN, n=7). In patients with SA, obstructive apneas during sleep were always associated with a prolongation of RT- as well as TpTe intervals. By contrast central apneas did not affect ventricular repolarisation significantly in the same patients. In the pig model for SA, 2min of acute tracheal occlusion with applied negative thoracic pressure resulted in a prolongation in RT- and TpTe-interval. These changes in ventricular repolarisation could be inhibited by atenolol as well as by RDN and were not influenced by parasympathetic blockade by atropine. By contrast hypoxia alone did not affect ventricular repolarisation. Intrathoracic pressure swings during obstructive apneas contribute to changes in ventricular repolarisation, which are not observed with central apneas. These changes are mainly driven by sympathetic activation and may represent mechanisms for increased occurrence of sudden cardiac death in obstructive SA.

Impact of Cardiac Resynchronization Therapy on Cardiac Electric Remodeling and its Clinical and Echocardiographic Correlation

Aim: impact of cardiac resynchronization therapy on cardiac electric remodeling and its clinical and echocardiographic correlation. Patients and Methods: 50 patients candidate for CRT were included and assessed before and 3 months after implantation by history taking, clinical examination, transthoracic echocardiogram, ECG and six minutes walk test. Results: 50 patients (35 males and 15 females, mean age 54.88±7.48 years) with implanted CRT. All patients were in sinus rhythm, QRS duration ≥120 ms and LBBB. There was clinical response to CRT as NYHA class improved p<0.001 and 6 min walk test p<0.001, electrocardiographic response where apart from RR interval, there were significant differences in QRSD, QT, QTc, QTd, and TPE between pre and post CRT measurements (P<0.001) and echocardiographic response as LV volume improved in 78%, EF in 14% and change (∆QRSD) significantly correlated with changes in NYHA, LVEDD, LVESD, and LVEF. (∆QTd) significantly correlated with change in NYHA but not with echocardiographic changes. But ( ∆TPE) significantly correlated with LVEDD, LVESD, LVEDV, LVESV, and LVEF but not with ∆NYHA. Area under the curve was 0.813 for ∆QRSD (p=0.005), 0.56 for ∆QT (p=0.56), 0.59 for ∆QTc (p=0.41), 0.823 for ∆QTd (p=0.004), and 0.8 for ∆TPE (p=0.007). ∆QTd of ≥-20 ms had highest sensitivity for predicting both clinical and Echocardiographic response, while ∆QRSD of ≥-20 ms had highest specificity. Conclusion: CRT induced reverse electric remodeling including depolarization and repolarization changes on unpaced ECG that was associated with reverse structural remodeling and clinical improvement.

A Rare Double Trigger for Takotsubo Cardiomyopathy

A woman admitted to the hospital for a massive Pulmonary Embolism, developed, at stable emodinamic condition, a complex clinical scenario characterized by Crohn disease exacerbation, chest pain and worsening dyspnea. The electrocardiogram presented non-specific repolarization changes. Echocardiogram showed new Left Ventricle akinesis of the apex and medium-apical segments, hyperkinetic basal segment with reduced ejection fraction. Coronarography showed not significant coronary artery disease and typical left ventricle apical ballooning. Left ventricle dysfunction recovered spontaneously in few days. This is the first case of Takotsubo Cardiomyopathy in course of pulmonary embolism and Crohn disease exacerbation. Summary: Takotsubo Cardiomyopathy is a syndrome characterized by acute regional systolic dysfunction of the left ventricle, frequently related to psycho-physical acute stress and usually reversible, in the absence of significant coronary artery disease. No cases have been reported of Takotsubo Cardiomyopathy associated with pulmonary embolism in the context of Crohn disease reacutization.

Cardiac rhythm, St-t wave-forms, and common electrocardiographic variants among healthy Nigerian children

Background: The cardiac rhythm depends on the source and mode of spread of the generated impulse. ST-T segment represents the repolarization phase of the action potential. Racial variability has been established in the morphology of the ST segment among the adult population and four waveforms has been described among Nigerian adults which are different from that of Caucasian adults; therefore, there may be differences among the pediatric population. Materials and Methods: This study was a further review of the electrocardiograph (ECG) of 650 apparently healthy primary school children aged 5-15 years, in Kano metropolis. Twelve-lead ECG was recorded, and interpretation was manually done. The subjects were categorized into three age groups namely 5-7, 8-11, and 12-15 years, respectively. The ST segment morphology was classified using Araoye's criteria. Results: Early repolarization changes were recorded in the 12-15 years age-group. The presence of ECG variants such as T-wave inversion in precordial leads V 1 -V 3 was reported and left axis deviation was documented in 0.4% of the 5-7 years age-group. Type I morphology was common in leads I, II, aVF, V 5 , V 6 . Type II morphology was common in leads I, II, V 4 R, V 5 , V 6 , while Type III morphology was common in leads V 4 R, V 5 , V 6 but Type IV morphology was seen mostly in V 1 . Conclusion: ST-segment elevation in the right precordial leads is a common finding in the pediatric ECG among Nigerian children; furthermore, T-wave inversion is also common in the right precordial leads and may extend way beyond precordial lead V 2 unlike in Caucasians.

Myocardial Dysfunction with Delayed Post-chemotherapy Enhancement Assessed in 3 Tesla Cardiac Magnetic Resonance imaging

Cardiomyopathy induced by myocardial fibrosis resulting from the use of doxorubicin and daunorubicin occurs in about 3% of patients, is dose-dependent, affects all age groups and is often irreversible.1 Cardiotoxicity can be acute, subacute or chronic.4 Acute or subacute cardiotoxicity is characterized by sudden changes in ventricular repolarization, changes in the Q-T interval, supraventricular and ventricular arrhythmias, acute coronary syndromes, pericarditis and myocarditis, usually observed from the onset up to 14 days after completion of treatment.4 The chronic cardiotoxicity can be differentiated into two types, according to the onset of clinical symptoms. The first subtype occurs within one year after the end of chemotherapy and the second usually occurs one year after the completion of chemotherapy. The most typical manifestation of chronic cardiotoxicity is systolic or diastolic ventricular dysfunction that may lead to congestive heart failure and cardiovascular death.4,5 The emergence of cardiovascular complications can determine interruption of chemotherapy, jeopardizing the cure or adequate control of cancer.6,7 It is worth noting that heart failure has a worse prognosis than many cancers and may seriously compromise the patient’s progress in treatment.8 The classical cardiotoxic effects are cumulative and are related to the dose, infusion rate, combination of drugs and hepatic and renal failure. In theory, any chemotherapeutic agent has the potential to cause toxicity. The cardiotoxicity of anthracyclines (doxorubicin, epirubicin and idarubicin) is characterized by a decline in left ventricular ejection fraction, occurs in 5% to 25% of the cases, begins with the first doses, and is related to cumulative dose, especially with doses above 400 mg/m2 of body surface.9 At this dose, there is a permanent myocardial damage characterized by myocyte apoptosis, resulting in fibrosis and loss of heart function.3

Prognostic Value of a New Marker of Ventricular Repolarization in Cirrhotic Patients.

BackgroundThere is still debate about the relationship between changes in ventricular repolarization on the surface electrocardiogram and cirrhosis severity.ObjectiveTo study the relationship between variables related to ventricular repolarization and the clinical severity of the cirrhotic disease.MethodsWe selected 79 individuals with hepatic cirrhosis, classified according to the Child-Pugh-Turcotte criteria (Child A, B, and C). We measured the QT and corrected QT (QTc) intervals, and the interval between the peak and the end of the T wave (TpTe), and we identified their minimum, maximum, and mean values in the 12-lead electrocardiogram. We also calculated the dispersion of the QT (DQT) and QTc (DQTc) intervals.ResultsIn 12 months of clinical follow-up, nine subjects underwent hepatic transplantation (Child A: 0 [0%]; Child B: 6 [23.1%]; Child C: 3 [18.8%]; p = 0.04) and 12 died (Child A: 3 [12.0%]; Child B: 4 [15.4%]; Child C: 5 [31.3%]; p = 0.002). No significant differences were observed between the cirrhotic groups related to the minimum, maximum, and mean values for the QT, QTc, TpTe, DQT, and DQTc intervals. A minimum TpTe interval ≤ 50 ms was a predictor for the composite endpoints of death or liver transplantation with a sensitivity of 90% and a specificity of 57% (p = 0.005). In the Cox multivariate analysis, the Child groups and a minimum TpTe of ≤ 50 ms were independent predictors of the composite endpoints.ConclusionThe intervals QT, QTc, DQT, DQTc, and TpTe have similar distributions between different severity stages in cirrhotic disease. The TpTe interval proved to be a prognostic marker in subjects with cirrhosis, regardless of disease severity (NCT01433848).

CPX-351 ((Cytarabine:Daunorubicin) Liposome Injection, (Vyxeos)) Does Not Prolong Qtcf Intervals, Requires No Dose Adjustment for Impaired Renal Function and Induces High Rates of Complete Remission in Acute Myeloid Leukemia

Introduction: CPX-351 is a liposomal formulation of cytarabine and daunorubicin encapsulated at a fixed 5:1 molar ratio. It is highly effective in patients with high-risk acute myeloid leukemia (AML). This study evaluated the impact of CPX-351 (100 units/m2) on cardiac repolarization.Methods: This open-label, Phase II, pharmacokinetic (PK) and pharmacodynamic (PD) study entered AML and acute lymphocytic leukemia (ALL) patients with good risk hepatic function (Child-Pugh scores <7), and normal cardiac function (LVEF≥50%, QTcF<470 ms). Cardiac repolarization changes were assessed using conventional ECG and Holter monitor recordings. PK was assessed during the first 21 days for total cytarabine, daunorubicin, Ara-U and daunorubicinol. The relationship between CPX-351 PK, QTcF, and renal function using the equation to calculate the estimated glomerular filtration rate (eGFR) was evaluated.Results: Twenty-six patients entered the study and 21 were evaluable for QT interval change from baseline. Evidence that CPX-351 prolongs the QTcF interval was not observed. The largest absolute and mean change from time-matched baseline was 12.56 and 8.03 ms, respectively (Day 1, hour 4). Mean QTcF change on Day 5 was unchanged from baseline. QTcF intervals >480 ms were never observed and no consistent QTcF intervals >450 ms were noted. Absolute QTcF increases between 30 and 60 ms were present in 4 of 25 patients and no changes >60 ms were observed. CPX-351 plasma concentration vs. time curves for day 1 and 5 exhibited a volume of distribution approximately equal to the plasma volume with prolonged single-exponential elimination half-lives for cytarabine and daunorubicin of ≥24 hours. The PK of CPX-351 was independent of renal function. Patients with moderately impaired (eGFR=30-59 mL/min/1.73m2) renal function exhibited similar drug exposure as those with mild and normal renal function.Table 1Impact of renal function impairment on Day 5 CPX-351 PK parameters (mean, %CV):AnalyteRenal FunctionCmax (ng/mL)AUClast (ng*hr/mL)AUCinf (ng*hr/mL)T1/2 (hr)CytarabineNormal (n=3)Mean593332893146290264142.5%CV28.768.86934.1Mild (n=7)Mean580713599512360669541.0%CV31.952.452.421.8Moderate (n=3)Mean573333149303315673838.0%CV46.650.750.621.9DaunorubicinNormal (n=3)Mean2596775464687086124.9%CV23.16365.356.0Mild (n=7)Mean28686865034102142030.5%CV43.943.543.625.3Moderate (n=3)Mean2193367154281473235.4%CV50.935.933.531.2Table 2 summarizes response and transplant outcomes. One of two ALL patients achieved CR and was transplanted. Among AML patients there were 7 CR and 2 CRi of which three went on to transplant. An additional four patients became morphologically leukemia free (MLF) and were transplanted before full documentation of CR was achieved. A large majority of patients given first-line treatment with CPX-351 responded or became suitable for transplant (10/13, 77%).Table 2206 Study EfficacyDiagnosisnResponseCR/CRiTransplanted in CR/CRiInduced MLF and TransplantedNo ResponseALL-Relapsed21/01/001AML-First Line de novo85/0012AML-First Line sAML51/21/111AML-Salvage111/01/028Conclusions: Clinically relevant prolongation of QTcF is not a feature of CPX-351 treatment. CPX-351 exposure was independent of renal function, indicating no need for dose adjustment when renal function is impaired. The high rate of complete remission and referral for transplant corroborate the high level of efficacy observed in earlier studies with CPX-351. DisclosuresStuart:Sunesis: Honoraria, Other: Advisory Board, Research Funding; Astellas Pharma, Inc: Research Funding. Michaelis:Incyte: Membership on an entity's Board of Directors or advisory committees; CTI Biopharma: Membership on an entity's Board of Directors or advisory committees; Wyeth: Membership on an entity's Board of Directors or advisory committees; Pfizer: Equity Ownership. Pentikis:Celator Pharmaceuticals: Consultancy. Alvarez:Celator Pharmaceuticals, Inc.: Employment, Equity Ownership. Mayer:Celator Pharmaceuticals, Inc.: Employment, Equity Ownership. Louie:Celator Pharmaceuticals, Inc.: Employment, Equity Ownership.

Peculiarities of cardiac performance in children with bronchial asthma against chronic tonsillitis.

Acomparativeassessmentofcardiacperformancebythedataofclinical-instrumentalexaminationof 50 patientsaged 5-15 yearswithpersistingformofpartially-controlledatopicbronchialasthmain the period between the attacks of the disease was made. Children were divided into two groups depending on presence of concomitant chronic tonsillitis (18 patients)or absence of the latter (32 patients). Inallcasesbythedataofspirographyinchildrenagainstchronictonsillitisintheperiodbetweentheattacksofthediseasetherewererevealedventillationdisordersinthelungsbyobstructiontype, thispromotedelevationofpressureinthepulmonaryartery.Only in this group of patients in 27,8% of cases pulmonary arterial hypertension of moderate severity was revealed. Byechocardiographydatainchildrenwithasthmaagainstchronictonsillitisreliablymoreoften(р&lt;0,01) therewasrevealeddecreaseofcontractilefunctionofmyocardiumoftheleftcardiacventricle; thiswascausedbythepresenceofmetabolicdisturbancesinthemyocardiuminthemajorityofcases(83,3%). These changes were registered on the electrocardiogram in the form of repolarisation changes of the ventricular complex.Presenceofconcomitantchronictonsillitisinchildrenwithbronchialasthmafavoredformationofpulmonaryhypertensionontheonesideandworseningofcontractileabilityofmyocardiumoftheleftcardiacventricleontheotherside;thisrequiredperformingtherapeutic-preventive measures for sanation of chronic infectious focus in the nasopharynx to prevent formation of chronic cardiac insufficiency during asthma course.

Abstract 14317: Kvβ2 Mediates Cardiac Repolarization and Injury: Role of Pyridine Nucleotides

Background: Voltage-gated potassium channel (Kv) β2 subunits (Kvβ2) belong to the aldoketo-reductase superfamily and associate with the Kv channel modulating its function. Also, Kvβ2 binds pyridine nucleotides (NAD[P] + /NAD[P]H) with high affinity altering Kv channel gating. However, the physiological relevance of Kvβ2 in cardiac health and disease is unknown. Hypothesis: We tested the hypothesis that Kvβ2 is essential to both basal and pyridine nucleotide mediated regulation of cardiac repolarization. Methods and Results: Kvβ2 knockout (KO) and wild type (Wt) mice were utilized for this study. ECG analysis showed prolonged QTc interval (74.7± 3.7 vs. 65.6 ± 3, n=3 , p&lt;0.05 ) in KO mice when compared to Wt. Monophasic action potential (MAP) data also showed prolonged duration (ms) at 50% repolarization level in KO mouse hearts vs. Wt (MAPD50; 13.2 ± 0.3 vs. 9.7 ± 0.6, n=5-6 , p&lt;0.05 ). To test the obligatory role of Kvβ2 in pyridine nucleotide modulation of cardiac repolarization, we exposed ex vivo perfused hearts or isolated cardiomyocytes to higher lactate levels. These data revealed that acute lactate exposure leads to significant but similar raise in NADH concentration [NADH] i in both KO and Wt heart tissue. However, marked repolarization deficits appeared only in Wt group when tested utilizing ex vivo perfused hearts (MAPD50 - Wt:11.5 ± 0.7 vs. 8.3 ± 0.5, p&lt;0.05 ; KO:12.6 ± 0.7 vs. 12± 0.5, p=0.5 , ms) or isolated myocytes (ΔAPD50 – Wt: 4.7±1.6 ms, p&lt;0.05 ; KO:1.5 ± 0.7 ms, p=0.1 ). Perfusion with high pyruvate levels returned both [NADH] i and MAPD50 to basal levels in Wt mouse hearts. Similarly, we observed that a 14 day isoproterenol treatment also leads to significant increase in cardiac [NADH] i , but only the Wt mouse hearts showed significant repolarization deficits; ex-MAPD50 (5.5 ± 1.6, p&lt; 0.01 ), when compared to no changes in KO (1.9 ± 0.9, p&lt; 0.1) . Conclusions: Our results suggest that Kvβ2 regulates cardiac repolarization. Further, the differential repolarization changes despite similar increases in cardiac [NADH] i indicates an obligatory role of Kvβ2 in the pyridine nucleotide modulation of cardiac repolarization.

Abstract 18417: Clinical Presentation, Cardiac Phenotype and Long Term Prognosis of Patients With Late Onset Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy

Introduction: The phenotypic features and clinical course of elderly Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy (ARVD/C) patients (age&gt; 50 years at diagnosis) is unknown. Methods: Demographic, phenotypic and genotypic data of 502 patients with ARVC diagnosis (2010 Task Force Criteria) from Johns Hopkins and Utrecht (NL) ARVD/C registries was obtained and long term clinical outcomes ascertained. Results: Late presentation was seen in 104 (21%) patients (38% with PKP2 mutation; no DSP or DSG2 mutation carrier) with 3% being ≥ 65 years at diagnosis. Sustained ventricular tachycardia (VT) is the major (43%) mode of presentation in the elderly while cardiac syncope is infrequent (p&lt;0.001). The elderly are significantly less likely to harbor a pathogenic mutation (53%; p=0.005), have precordial T wave repolarization changes (p&lt;0.001) and have lower ventricular ectopy burden (median count 1503 vs 2497; p=0.026) compared to younger patients. In the elderly, over 7±5 years of follow up, 68(65%) patients experienced sustained ventricular arrhythmias with similar (p=0.08) arrhythmia free survival at 5 years of follow up (73% vs.60% in younger). LV dysfunction and heart failure was seen in 24(32%) and 15(14%) patients respectively without need for cardiac transplantation. Male gender (OR 2.12, 95%CI (1.3-3.45); p=0.002), absence of a pathogenic mutation (OR 1.94, 95%CI (1.20, 3.12); p=0.006) and family member status (OR 2.09, 95%CI (1.24, 3.51); P=0.006) were independently associated with late presentation. In the elderly, EP study inducibility (&lt;0.001), major RV structural disease (p=0.022), absent family history (p&lt;0.001), male gender (p=0.002) and pathogenic mutation (p=0.001) were associated with increased risk of ventricular arrhythmias while ECG abnormalities and ventricular ectopy (p=0.489) were not. Conclusion: One fifth of all ARVD/C patients present after 50 years of age, often with sustained VT and are less likely to have prior syncope or identifiable pathogenic mutation. In ARVD/C, late presentation does not confer a benign prognosis and is associated with high arrhythmic risk. Electrocardiographic changes and ventricular ectopy are significantly less common in the elderly and are not associated with arrhythmic events.

Takotsubo syndrome and polymorphic ventricular tachycardia: The chicken or the egg

To the Editor, I read with great interest the study by Hojo et al. [1], published in the Journal, about a 74-year-old woman with bouts of polymorphic ventricular tachycardia (PVT) in the setting of Takotsubo syndrome (TTS) who was found to be hypokalemic and had prominent T-wave and J-wave electrical alternans, and mechanical alternans. The following are some thoughts and questions for the authors’ kind consideration: (1) It is conceivable that TTS came first, as the authors propose, followed by J-wave and T-wave alternans, and QTc interval prolongation, which led to PVT, with perhaps some further facilitation caused by the underlying hypokalemia. However, it is also possible that the patient had bouts of PVT precipitated by the underlying hypokalemia (although later hypokalemia was not associated with electrocardiographic repolarization changes), J-wave and T-wave alternans, and QTc interval prolongation, which in turn led to the physical stress that triggered the TTS. (2) Why did the patient’s hypokalemia take 56 h to control? Was there any reason that larger potassium infusions, of course under close potassium blood level monitoring, were not implemented? (3) The mechanical alternans could have been a phenomenon previously encountered in association with T-wave alternans and in the absence of heart failure, or could have been an epiphenomenon of the precipitated left ventricular failure due to TTS. (4) Although this patient’s hypokalemia was attributed to the hydrocortisone “she had taken for pituitary adrenal insufficiency after surgery for a pituitary tumor” [1], it is conceivable that hypokalemia was also further aggravated by the underlying circulating catecholamines (particularly epinephrine), and thus poorly responded to the potassium infusion. Both, TTS [2] and hypokalemia [3], [4] have been shown to be mediated by specific β2-adrenoreceptor stimulation.

Электрокардиографические показатели электрической нестабильности миокарда у больных синдромом обструктивного апноэ-гипопноэ во время сна и впервые выявленной артериальной гипертензией

Objective. To study the rate of long QTc and JTc intervals in sleep-wakefulness cycle, and also their relationship with severity of obstructive sleep apnea-hypopnea syndrome (OSA) in patients with newly diagnosed hypertension (HTN). Design and methods. 24‑hour multifunctional monitoring was conducted in 59 male patients (age 38,0 ± 7,7 years old; body mass index 33,8 ± 5,4 kg/m 2) with elevated office blood pressure, who did not receive any medications. All patients had two or more risk factors of HTN. Organ damage was identified in 12 (20 %) patients. The long QTc interval was defined as 450 msec or more, automatic analysis was performed using 8‑lead dynamic ECG. Results. OSA was diagnosed in 40 (68 %) patients: 17 patients had mild sleep apnea (apneahypopnea index, AHI, from 5 to 14 episodes per hour), the rest of the patients had moderate and severe OSA (AHI from 18 to 97 episodes per hour). Nineteen (32 %) patients without OSA were included in the comparison group (AHI less than 5 episodes per hour). There was no differences in average heart rate during assessed time periods between the groups. There was a direct positive correlation between duration of QTc and JTc calculated separately for periods of wakefulness, sleep and AHI and hypoxemia index. Conclusions. More than 50 % of patients with newly diagnosed AH and OSA without associated cardiovascular diseases demonstrate changes in myocardial repolarization throughout sleep-wakefulness cycle. These changes are associated with the number of apneas/hypopneas and the severity of hypoxemia during sleep