Sara Reda

Effects of renal sympathetic denervation on arterial stiffness and central hemodynamics in patients with resistant hypertension.

OBJECTIVES This study investigated the effect of catheter-based renal sympathetic denervation (RD) on central hemodynamics in patients with resistant hypertension. BACKGROUND High central blood pressure (BP) increases cardiovascular events and mortality independently of peripheral BP. The effect of RD on central BP is unclear. METHODS A total of 110 patients underwent bilateral RD. Radial artery applanation tonometry and pulse wave analysis were used to derive central aortic pressure and hemodynamic indices at baseline and 1, 3, and 6 months after ablation. Ten patients with resistant hypertension not undergoing RD served as controls. RESULTS RD significantly reduced mean central aortic BP from 167/92 mm Hg to 149/88 mm Hg, 147/85 mm Hg, and 141/85 mm Hg at 1, 3, and 6 months (p < 0.001), respectively. Aortic pulse pressure decreased from 76.2 ± 23.3 mm Hg to 61.5 ± 17.5 mm Hg, 62.7 ± 18.1 mm Hg, and 54.5 ± 15.7 mm Hg 1, 3, and 6 months after RD (p < 0.001), respectively. Six months after RD aortic augmentation and augmentation index were significantly reduced by -11 mm Hg (p < 0.001) and -5.3% (p < 0.001), respectively. Carotid to femoral pulse wave velocity showed a significant reduction from 11.6 ± 3.2 m/s to 9.6 ± 3.1 m/s at 6 months (p < 0.001). Consistently, ejection duration and aortic systolic pressure load were significantly diminished, indicating improvement of cardiac work load by RD. No significant changes were obtained in control patients. CONCLUSIONS Besides the known effect of RD on brachial blood pressure, the study showed for the first time that this novel approach significantly improves arterial stiffness and central hemodynamics, which might have important prognostic implications in patients with resistant hypertension at high cardiovascular risk.

Cardiac arrest due to long QT syndrome associated with excessive consumption of energy drinks

Amphetamines 1000 Negative Barbiturates 300 Negative Benzodiazepines 300 Negative Cannabinoids 50 Negative Cocaine 300 Negative MDMA 500 Negative Metamphetamine 1000 Negative Methadone 300 Negative The congenital form of long QT syndrome is characterized by a prolonged QT interval in the electrocardiogram (ECG) and is complicated by episodes of polymorphic ventricular tachycardia known as torsades de pointes (TdP). Patients with long QT syndrome 1 (LQTS-1) typically may suffer cardiac arrest during exercise. Based on these observations beta-blocker therapy is recommended in these patients to reduce the maximal heart rate and blunt the effects of adrenaline. Energy drinks contain high doses of taurine (an amino acid), caffeine and glucuronolactone (a glucose metabolite), neither of which is considered to have significant toxicity. We report a case of a 22 year old female with out of hospital cardiac arrest (OHCA) due to initial torsades de pointes tachycardia secondary degenerating to ventricular fibrillation. Sudden cardiac death occurred without prodrome in a discotheque. Basic life support was performed immediately. After 15 minutes of resuscitation with fractionated administration of 3 mg adrenaline return of spontaneous circulation (ROSC) could be achieved after the patient received five 360 Joule shocks by the emergency medical services personnel. Initial ECG showed torsades de pointes tachycardia, which degenerated during resuscitation to ventricular fibrillation. After ROSC the patient was admitted to our intensive care unit. Acute cardiac catheterization excluded coronary macroangiopathy or coronary anomalies. Cardiac ventriculography revealed a normal ejection fraction of 69. Echocardiography showed normal cardiac function without any pathologic pattern. Furthermore, no pericardial effusion was found. Results of a urinary screen for drug or alcohol misuse were negative (Table 1). Potassium level at admission was normal (4.4 mmol/l). Abnormal

Postprocedural Atrial Fibrillation After Transcatheter Aortic Valve Implantation Versus Surgical Aortic Valve Replacement

BACKGROUND Transcatheter aortic valve implantation (TAVI) represents an alternative option for elderly patients with severe aortic valve stenosis who are denied surgical aortic valve replacement (SAVR) because of high perioperative risk. The impact of TAVI on postprocedural atrial fibrillation is undefined. METHODS In a single-center analysis, we assessed clinical data, preoperative risk scores (Society for Thoracic Surgeons score, logistic European System for Cardiac Operative Risk Evaluation), preprocedural electrocardiograms, and 72-hour postprocedural rhythm monitoring of 170 patients undergoing TAVI (n=84) or SAVR (n=86). In a subanalysis, transapical (n=43) and transfemoral TAVI (n=41) were compared. RESULTS Expectedly, TAVI patients were significantly older, presented with more severe symptoms, had higher Society for Thoracic Surgeons score, higher logistic European System for Cardiac Operative Risk Evaluation score, and revealed more frequently intermittent atrial fibrillation compared with SAVR patients. Despite this more compromised health state, prevalence of postprocedural atrial fibrillation was significantly lower in the TAVI group (6.0%, versus 33.7% after SAVR, p<0.05). More than two thirds of TAVI patients but no SAVR patient with atrial fibrillation in preprocedural electrocardiograms had stable sinus rhythm during 72-hour postprocedural monitoring. Notably, no atrial fibrillation was observed after transfemoral TAVI. Whereas atrial fibrillation onset in the SAVR group predominantly occurred on postoperative day 3, atrial fibrillation onset after transapical TAVI was obtained within the first 24 hours after the intervention. CONCLUSIONS Our results indicate that TAVI, compared with SAVR, reduces the risk of periprocedural atrial fibrillation. Furthermore, preprocedural atrial fibrillation may be converted into sinus rhythm particularly after transfemoral TAVI, suggesting an impact of decreased intracardiac pressures in the absence of adverse periprocedural factors that might promote atrial fibrillation.

Clinical Impact of Atrial Fibrillation in Patients with Pulmonary Hypertension

Background Pulmonary hypertension (PH) is associated with progressive impairment of right ventricular function, reduced exercise capacity and a poor prognosis. Little is known about the prevalence, clinical manifestation and impact of atrial fibrillation (AF) on cardiac function in PH. Methods In a four year single-centre retrospective analysis 225 patients with confirmed PH of various origins were enrolled to investigate the prevalence of AF, and to assess the clinical manifestation, 6-minute walk distance, NT-proBNP levels, echocardiographic parameters and hemodynamics obtained by right heart catheterization in PH with AF. Results AF was prevalent in 31.1%. In patients with PH and AF, parameters of clinical deterioration (NYHA/WHO functional class, 6-minute walk distance, NT-proBNP levels) and renal function were significantly compromised compared to patients with PH and sinus rhythm (SR). In the total PH cohort and in PH not related to left heart disease occurrence of AF was associated with an increase of right atrial pressure (RAP) and right atrial dilatation. While no direct association was found between pulmonary artery pressure (PAP) and AF in these patients, right ventricular function was reduced in AF, indicating more advanced disease. In PH due to left heart failure the prevalence of AF was particularly high (57.7% vs. 23.1% in other forms of PH). In this subgroup, left atrial dilatation, increase of pulmonary capillary wedge pressure, PAP and RAP were more pronounced in AF than in SR, suggesting that more marked backward failure led to AF in this setting. Conclusion PH is associated with increased prevalence of AF. Occurrence of AF in PH indicates clinical deterioration and more advanced disease.

By Regulating Mitochondrial Ca2+-Uptake UCP2 Modulates Intracellular Ca2+.

Introduction The possible role of UCP2 in modulating mitochondrial Ca2+-uptake (mCa2+-uptake) via the mitochondrial calcium uniporter (MCU) is highly controversial. Methods Thus, we analyzed mCa2+-uptake in isolated cardiac mitochondria, MCU single-channel activity in cardiac mitoplasts, dual Ca2+-transients from mitochondrial ((Ca2+)m) and intracellular compartment ((Ca2+)c) in the whole-cell configuration in cardiomyocytes of wild-type (WT) and UCP2-/- mice. Results Isolated mitochondria showed a Ru360 sensitive mCa2+-uptake, which was significantly decreased in UCP2-/- (229.4±30.8 FU vs. 146.3±23.4 FU, P<0.05). Single-channel registrations confirmed a Ru360 sensitive voltage-gated Ca2+-channel in mitoplasts, i.e. mCa1, showing a reduced single-channel activity in UCP2-/- (Po,total: 0.34±0.05% vs. 0.07±0.01%, P<0.05). In UCP2-/- cardiomyocytes (Ca2+)m was decreased (0.050±0.009 FU vs. 0.021±0.005 FU, P<0.05) while (Ca2+)c was unchanged (0.032±0.002 FU vs. 0.028±0.004 FU, P>0.05) and transsarcolemmal Ca2+-influx was inhibited suggesting a possible compensatory mechanism. Additionally, we observed an inhibitory effect of ATP on mCa2+-uptake in WT mitoplasts and (Ca2+)m of cardiomyocytes leading to an increase of (Ca2+)c while no ATP dependent effect was observed in UCP2-/-. Conclusion Our results indicate regulatory effects of UCP2 on mCa2+-uptake. Furthermore, we propose, that previously described inhibitory effects on MCU by ATP may be mediated via UCP2 resulting in changes of excitation contraction coupling.

UCP2 Modulates Cardioprotective Effects of Ru360 in Isolated Cardiomyocytes during Ischemia

Introduction: Ruthenium 360 (Ru360) has been shown to induce cardioprotective mechanisms in perfused hearts. The agent is a specific blocker of the main cardiac mitochondrial uptake mechanism, the mitochondrial calcium uniporter (MCU). UCP2, a mitochondrial membrane protein, which influences cardiac ROS formation was reported to interact with the MCU. Methods: To prove whether Ru360 affects ischemic cell injury on the singular cell level, cell viability (CV) in isolated cardiomyocytes from wild type mice (WT) was measured in a model of pelleting hypoxia (PH). To explore a possible influence of UCP2 on cellular survival, as well as on Ru360 function, cardiomyocytes from UCP2−/− mice were investigated. Results: During PH, Ru360 significantly improved CV in WT cardiomyocytes (Control 26.32% ± 1.58% vs. PH 13.60% ± 1.20% vs. PH+Ru360 19.98% ± 0.98%, n = 6; p < 0.05). No differences in the rate of apoptosis were observed in UCP2−/− vs. WT. In UCP2−/− cardiomyocytes, Ru360 reduced the rate of cell death. However, the effect was less pronounced compared to WT cardiomyocytes. Conclusion: Ru360 significantly reduces hypoxic cell injury by preventing single cell apoptosis in WT cardiomyoctes. UCP2 does not affect cell survival in hypoxic cardiomyocytes, but it might modulate cardioprotective effects of Ru360 during ischemia.

UCP3 Regulates Single-Channel Activity of the Cardiac mCa1.

Mitochondrial Ca2+ uptake (mCa2+ uptake) is thought to be mediated by the mitochondrial Ca2+ uniporter (MCU). UCP2 and UCP3 belong to a superfamily of mitochondrial ion transporters. Both proteins are expressed in the inner mitochondrial membrane of the heart. Recently, UCP2 was reported to modulate the function of the cardiac MCU related channel mCa1. However, the possible role of UCP3 in modulating cardiac mCa2+ uptake via the MCU remains inconclusive. To understand the role of UCP3, we analyzed cardiac mCa1 single-channel activity in mitoplast-attached single-channel recordings from isolated murine cardiac mitoplasts, from adult wild-type controls (WT), and from UCP3 knockout mice (UCP3–/–). Single-channel registrations in UCP3−/− confirmed a murine voltage-gated Ca2+ channel, i.e., mCa1, which was inhibited by Ru360. Compared to WT, mCa1 in UCP3−/− revealed similar single-channel characteristics. However, in UCP3−/− the channel exhibited decreased single-channel activity, which was insensitive to adenosine triphosphate (ATP) inhibition. Our results suggest that beyond UCP2, UCP3 also exhibits regulatory effects on cardiac mCa1/MCU function. Furthermore, we speculate that UCP3 might modulate previously described inhibitory effects of ATP on mCa1/MCU activity as well.

Diagnose & Therapie der diastolischen Herzinsuffizienz

ZusammenfassungIn den letzten Jahren hat sich herausgestellt, dass die diastolische Herzinsuffizienz sehr viel häufiger auftritt als vermutet. Bei mehr als 50 % der chronisch herzinsuffizienten Patienten ist vor allem die diastolische Funktion beeinträchtigt, während die Pumpfunktion erhalten ist. Hauptursache dafür ist eine linksventrikuläre Hypertrophie, oft infolge einer arteriellen Hypertonie. Aufgrund der hohen Morbidität und Mortalität muss die Diagnose möglichst früh gestellt werden. Die Grunderkrankung sollte nach Möglichkeit kausal behandelt werden. Bisher wurden Patienten mit diastolischer Herzinsuffizienz aber oft explizit von Therapiestudien ausgeschlossen. Daher gibt es derzeit zu wenige Daten für eine evidenzbasierte Behandlung.

Erratum zu: Diagnose & Therapie der diastolischen Herzinsuffizienz

In der letzten Ausgabe hat sich im Beitrag „Diagnose & Therapie der diastolischen Herzinsuffi zienz“ ein Fehler eingeschlichen. Die Abbildung des diagnostischen Algorithmus bei chronischer Herzinsuffi zienz (Abb. 1) wurde im Heft nicht abgedruckt. Dadurch trugen die nachfolgenden Abbildungen (Abb. 2, 3) ebenfalls eine falsche Beschriftung. Der Fehler wurde online korrigiert. Den korrigierten Beitrag fi nden sie online unter www.springermedizin.de/kurse-cme. Wir bitten den Fehler zu entschuldigen.

Neue Tyrosinkinase- und EGFR-Inhibitoren in der Tumortherapie

ZusammenfassungMonoklonale Antikörper und Tyrosinkinaseinhibitoren gehören zu den etablierten Therapien von Malignomen. Sie beeinflussen bzw. modulieren unterschiedliche Signaltransduktionswege, wodurch organspezifische Nebenwirkungen entstehen. Die Therapiedauer beträgt zumeist Monate bis Jahre, sodass im Verlauf kardiovaskuläre Nebenwirkungen wie myokardiale Dysfunktion bis hin zur chronischen Herzinsuffizienz sowie eine arterielle Hypertonie, Thrombosen und Arrhythmien auftreten können. Die Manifestationen der kardialen Nebenwirkungen sind individuell verschieden und reichen von einer asymptomatischen Reduktion der linksventrikulären Pumpfunktion bis zur symptomatischen akuten Herzinsuffizienz oder zum akuten Koronarsyndrom. Zu den Substanzen mit vermehrten kardiovaskulären Nebenwirkungen gehören die Anti-HER2-Therapeutika in Kombination mit Anthrazyklinen und die Angiogeneseinhibitoren. Bei einigen Präparaten fehlen zurzeit noch große randomisierte Langzeitbeobachtungen, bevor eine Kardiotoxizität sicher ausgeschlossen werden kann. Bei kardialen Nebenwirkungen oder vorbestehender kardiovaskulärer Erkrankung zu Therapiebeginn sollte die Behandlung zusammen mit einem Kardiologen erfolgen. Im Falle von Nebenwirkungen sollte interdisziplinär entschieden werden, ob eine symptomspezifische Therapie erfolgen sollte oder die Malignomtherapie beendet oder umgestellt werden muss.AbstractCardiotoxicity is a serious side effect of targeted molecular therapies in cancer treatment. Monoclonal antibodies and tyrosine kinase inhibitors are known to be potent therapies in various neoplastic diseases due to inhibition of specific signal transduction pathways. Although targeted therapies are considered to be less toxic and better tolerated than common chemotherapies certain cardiac side effects have been observed. Cardiac toxicity may range from asymptomatic reduction of left ventricular function to life-threatening events like heart failure and acute coronary syndrome. Further side effects are arterial hypertension, thrombosis and arrhythmias. Cardiovascular side effects are common for anti-HER2 therapy in combination with anthracyclines and for inhibitors of angiogenesis. In these patients careful cardiac monitoring is warranted. Because of missing randomized long-term follow-ups, information about cardiac side effects is limited in newly developed targeted molecular therapies. In case of cardiac side effects or preexisting cardiac disease before therapy initiation, assessments by a cardiologist throughout the course of treatment are important. For patients with severe cardiac side effects, discontinuation of treatment is warranted; in case of asymptomatic cardiac side effects symptom-specific therapy should be performed.Cardiotoxicity is a serious side effect of targeted molecular therapies in cancer treatment. Monoclonal antibodies and tyrosine kinase inhibitors are known to be potent therapies in various neoplastic diseases due to inhibition of specific signal transduction pathways. Although targeted therapies are considered to be less toxic and better tolerated than common chemotherapies certain cardiac side effects have been observed. Cardiac toxicity may range from asymptomatic reduction of left ventricular function to life-threatening events like heart failure and acute coronary syndrome. Further side effects are arterial hypertension, thrombosis and arrhythmias. Cardiovascular side effects are common for anti-HER2 therapy in combination with anthracyclines and for inhibitors of angiogenesis. In these patients careful cardiac monitoring is warranted. Because of missing randomized long-term follow-ups, information about cardiac side effects is limited in newly developed targeted molecular therapies. In case of cardiac side effects or preexisting cardiac disease before therapy initiation, assessments by a cardiologist throughout the course of treatment are important. For patients with severe cardiac side effects, discontinuation of treatment is warranted; in case of asymptomatic cardiac side effects symptom-specific therapy should be performed.