Behrouz Kherad

Heart failure with preserved ejection fraction: current management and future strategies

About 50% of all patients suffering from heart failure (HF) exhibit a reduced ejection fraction (EF ≤ 40%), termed HFrEF. The others may be classified into HF with midrange EF (HFmrEF 40–50%) or preserved ejection fraction (HFpEF, EF ≥ 50%). Presentation and pathophysiology of HFpEF is heterogeneous and its management remains a challenge since evidence of therapeutic benefits on outcome is scarce. Up to now, there are no therapies improving survival in patients with HFpEF. Thus, the treatment targets symptom relief, quality of life and reduction of cardiac decompensations by controlling fluid retention and managing risk factors and comorbidities. As such, renin–angiotensin–aldosterone inhibitors, diuretics, calcium channel blockers (CBB) and beta-blockers, diet and exercise recommendations are still important in HFpEF, although these interventions are not proven to reduce mortality in large randomized controlled trials. Recently, numerous new treatment targets have been identified, which are further investigated in studies using, e.g. soluble guanylate cyclase stimulators, inorganic nitrates, the angiotensin receptor neprilysin inhibitor LCZ 696, and SGLT2 inhibitors. In addition, several devices such as the CardioMEMS, interatrial septal devices (IASD), cardiac contractility modulation (CCM), renal denervation, and baroreflex activation therapy (BAT) were investigated in different forms of HFpEF populations and some of them have the potency to offer new hopes for patients suffering from HFpEF. On the basic research field side, lot of new disease-modifying strategies are under development including anti-inflammatory drugs, mitochondrial-targeted antioxidants, new anti-fibrotic and microRNA-guided interventions are under investigation and showed already promising results. This review addresses available data of current best clinical practice and management approaches based on expert experiences and summarizes novel approaches towards HFpEF.

Heart Failure with Preserved Ejection Fraction and Future Pharmacological Strategies: a Glance in the Crystal Ball

Purpose of ReviewThe current definition of heart failure is mainly based on an inappropriate measure of cardiac function, i.e., left ventricular ejection fraction (LVEF). The initial sole entity, heart failure with reduced ejection fraction (HFrEF, LVEF <40%), was complemented by the addition of heart failure with preserved ejection fraction (HFpEF, LVEF ≥50%) and most recently, heart failure with mid-range ejection fraction (HFmrEF, LVEF 40–49%). Initially, HFpEF was believed to be a purely left ventricular diastolic dysfunction. Pathophysiological concepts of HFpEF have changed considerably during the last years. In addition to intrinsic cardiac mechanisms, the heart failure pathogenesis is increasingly considered as driven by non-cardiac systemic processes including metabolic disorders, ischemic conditions, and pro-inflammatory/pro-fibrotic or immunological alterations. Presentation and pathophysiology of HFpEF is heterogeneous, and its management remains a challenge since evidence of therapeutic benefits is scarce. Up to now, there are no therapies improving survival in patients with HFpEF.Recent FindingsSeveral results from clinical and preclinical interventions targeting non-cardiac mechanisms or non-pharmacological interventions including new anti-diabetic or anti-inflammatory drugs, mitochondrial-targeted anti-oxidants, anti-fibrotic strategies, microRNases incl. antagomirs, cell therapeutic options, and high-density lipoprotein-raising strategies are promising and under further investigation.SummaryThis review addresses mechanisms and available data of current best clinical practice and novel approaches towards HFpEF.

Low permanent pacemaker rates following Lotus device implantation for transcatheter aortic valve replacement due to modified implantation protocol

BACKGROUND Conduction disturbances requiring permanent pacemaker implantation following transcatheter aortic valve replacement (TAVR) are a common problem. Pacemaker implantation rates after TAVR appear to be higher compared to conventional aortic valve replacement. The aim of this study was to analyze whether a high annulus implantation conveys the benefit of a decreased rate of permanent pacemaker implantation while being safe and successful according to Valve Academic Research Consortium 2 (VARC2)-criteria. METHODS A total of 23 patients with symptomatic severe aortic valve stenosis, an aortic annulus of 19-27 mm and at high risk for surgery were treated with the Lotus valve. In all patients the valve was implanted in a high annulus position via femoral access. The primary device performance endpoint was VARC2-defined device success after 30 days and the primary safety endpoint was the need for permanent pacemaker implantation. RESULTS The mean age was 73.23 ± 7.65 years, 46% were female, 38% were New York Heart Association class III/IV at baseline. Thirty-day follow-up data were available for all patients. The VARC2-defined device success rate after 30 days was 22/23 (96%). 2/21 (10%) patients required a newly implanted pacemaker due to 3rd degree atrioventricular block. 25% of the patients developed a new left bundle branch block after valvuloplasty or device implantation. 21 of the 23 patients (96%) had no other signs of conduction disturbances after 30 days. CONCLUSIONS The approach of the modified implantation technique of Lotus TAVR device was safe and effective. The incidence of need for a permanent pacemaker following TAVR could be significantly reduced due to adopted implantation protocol.

[Cardiovascular risk of androgen deprivation therapy for treatment of hormone-dependent prostate cancer : Differences between GnRH antagonists and GnRH agonists].

ZusammenfassungAus mehreren Studien geht hervor, dass das Absenken der Testosteronspiegel bei Patienten mit Prostatakarzinom im Rahmen einer Androgendeprivationstherapie (ADT) mit einem erhöhten Risiko für das Auftreten kardiovaskulärer Ereignisse einhergehen kann, was besonders beim Einsatz von GnRH („gonadotropin-releasing hormone“)-Agonisten aufgefallen ist. Eine ADT mit GnRH-Antagonisten muss jedoch in diesem Zusammenhang aufgrund ihres anderen Wirkmechanismus separat betrachtet werden. In dieser Übersichtsarbeit werden Ursachen für das Auftreten kardiovaskulärer Ereignisse unter ADT diskutiert, die Unterschiede zwischen GnRH-Agonisten und GnRH-Antagonisten im Hinblick auf ihren Wirkmechanismus erläutert, relevante Studien präsentiert und praktische Empfehlungen für den Arzt abgeleitet. Dazu wurde eine Literaturrecherche zu Veröffentlichungen im Zeitraum von 2005 bis September 2015 durchgeführt. Diese ergab, dass Patienten mit Prostatakarzinom unter GnRH-Antagonisten ein geringeres kardiovaskuläres Risiko aufwiesen als Patienten, die mit GnRH-Agonisten behandelt wurden. Dies galt insbesondere für Patienten, die kardiovaskulär erkrankt waren. Die unterschiedlichen Wirkmechanismen beider Substanzklassen liefern erste Erklärungen für das geringere kardiovaskuläre Risiko unter GnRH-Antagonisten. Patienten mit kardiovaskulärer Vorerkrankung oder dem Risiko für ein kardiovaskuläres Ereignis sollten vorzugsweise mit einem GnRH-Antagonisten behandelt werden.AbstractBackgroundSeveral studies have indicated that reduction of testosterone levels in patients with prostate cancer undergoing androgen deprivation therapy (ADT) with gonadotropin-releasing hormone (GnRH) agonists can be associated with an increased risk of cardiovascular events. The GnRH antagonists have a different mode of action compared with GnRH agonists and may be preferred in ADT for patients with cardiovascular disease.ObjectiveThis review article discusses potential mechanisms underlying the development of cardiovascular events associated with ADT when using GnRH agonists and explains the differences in mode of action between GnRH agonists and GnRH antagonists. Additionally, relevant studies are presented and practical recommendations for the clinical practice are provided.Material and methodsA literature search was performed. Full publications and abstracts published in the last 10 years up to September 2015 were considered to be eligible.ResultsThe GnRH antagonists were associated with a decreased risk of cardiovascular events compared with GnRH agonists in prostate cancer patients undergoing ADT and particularly in patients with cardiovascular risk factors or a history of cardiovascular disease. This decrease may be due to the different mode of action of GnRH antagonists compared with GnRH agonists.ConclusionProstate cancer patients with either cardiovascular disease or an increased risk of experiencing a cardiovascular event undergoing ADT should be preferentially treated with GnRH antagonists.

DCB meets DES

The drug-coated balloon (DCB) technique hasmainly been tested in the clinical scenario of in-stent restenosis, where it demonstrated a similar clinical efficacy to additional drug-eluting stent (DES) implantation [1]. Recently, several studies have shown that the usage of DCB in de novo lesions might be beneficial, including in small-vessel disease [2] and bifurcation lesions [3]. DCB offers numerous advantages including rapid and uniform antiproliferative drug transfer to the arterial wall, without the need for permanent metal struts in the vessel wall, thereby avoiding the effect of stents on long-term vascular healing and reducing the duration of double antiplatelet therapy. However, DCB usage requires careful vessel preparation, which implies a change in strategies. When using DCBs, vessel preparation is mandatory and, according to the recommendations of the German Consensus Group on DCB interventions [4], it involves pre-dilatation of the stenotic artery with an angioplasty balloon. If the lesion shows a flow-limiting dissection (thrombolysis in myocardial infarction [TIMI] score ≤ 2), i. e., a dissection of type C–F according to the National Heart, Lung, and Blood Institute classification [5], or a residual stenosis of >30% after initial balloon inflation, a strategy change is recommendedwith the implantation of a DES according to the usual recommendations [6]. Thus, a DCB should be selected only after successful pre-dilatation. It is important to note that the DCB is only used to deliver the drug locally, and should not succeed the pre-dilatation balloon in diameter. If, nevertheless, a significant dissection and/or a residual stenosis of >30% after DCB occurs, bare metal stent (BMS) spot stenting is recommended, again avoiding geographical mismatch. This is to avoid combination of paclitaxel (DCB) with a limus agent (DES), the effects of which on coronary vasculature are largely unknown. However, this might yield inferior results, given the well-demonstrated superior efficacy ofDES-containing limus analogues compared with paclitaxel-coated DES. Ong et al. recently showed that the combinationofDCBwithDESappears to be safe and effective, at least in a porcine model at 28 days of follow-up [7]. Previously, a small study analyzed 69 patients with de novo lesions treated either with a DCB alone or a combination of a DEB andDES and showed that the 7.4% of patients (n =5) treated with DCB and DES as bail-out had outcome rates comparable to those who were treated with DES alone at the 2-year follow-up (major adverse cardiac events = 20.8% vs. 22.7%, p = 0.74; target vessel revascularization (repeat PCI or CABG of the target vessel) = 14.8% vs. 11.5%, p = 0.44; target lesion revascularization = 9.6% vs. 9.3%, p = 0.84) [8]. Intheirpaper,Moketal. provideadditional insights into this matter [9]. They analyzed 76 patients who were treated with either BMS or a DES after DCB employment (10% for recoil, 52% for a dissection, and 38% for other reasons). Of these patients, 52 were treated with a BMS and 24 with a DES, and at the 1-year follow-up there were nomajor differences in terms of clinical endpoints (major adverse cardiac events, CV death, myocardial infarction, or target lesion revascularization). Angiographically, only 15 patients in the PCB + BMS group and eight patients in the PCB + DES group had follow-up angiograms, of whom five (33.3%) and one (12.5%) patients, respectively, showed significant in-stent restenosis. The authors therefore concluded that that use of DES following PCB appeared to be clinically safe and effective in their cohort. In conclusion, DCB offers possible advantages in a subset of coronary anatomies. When using DCB, careful vessel preparation is mandatory. The turning point in a DCB–percutaneous coronary intervention concept is the angiographic result after vessel preparation. If angioplasty has yielded a vessel dissection or suboptimal vessel reparation, subsequent stent implantation is recommended. Once vessel preparation has yielded an optimal result, the DCB can be used as planned solely for local delivery of the drug. If, nevertheless, the drug delivery has resulted in flow-limiting dissection of the vessel, the current study and the results in animal models indicate that bailout stenting with a DES is safe and efficient.

9-month results of polymer-free sirolimus eluting stents in young patients compared to a septuagenarian and octogenarian all-comer population

OBJECTIVES To evaluate the 9-month safety and efficacy of polymer-free sirolimus eluting drug eluting stents in septuagenarians and octogenarians. METHODS An all-comer, worldwide single armed trial (ClinicalTrials.gov Identifier NCT02629575) was conducted to demonstrate the safety and efficacy of an ultra-thin strut, polymer-free sirolimus eluting stent (PF-SES). The primary endpoint was the 9-month target revascularization rate (TLR). Secondary endpoints included the rates of major adverse cardiac events (MACE), stent thrombosis (ST) and bleeding (BARC) in septuagenarians (≥70 years, <80 years), and in octogenarians (≥80 years) to be compared to the younger patient group (<70 years). RESULTS A total of 1607 patients were treated with PF-SES in the sub-70-year-old age group, 694 in septuagenarians, and 371 in the octogenarian patient group. At 9 months, the MACE rates were 7.2% in octogenarians, 5.3% in septuagenarians, and 3.0% in the younger patient group (P = 0.001). These were mostly driven by all-cause mortality (4.4% vs 1.9% vs 0.6%, P < 0.001) while the TLR rates were only numerically lower in the younger age group (P = 0.080). BARC 1-5 bleeding events were more frequent in the older age group (1.9% vs 2.7% vs 4.6%, P = 0.012) whereas the rates for ST were not different (0.7% vs 0.6% vs 0.6%, P = 0.970). CONCLUSIONS In octogenarians treated with PF-SES, the rates for MACE, overall mortality, and bleeding are higher as compared to the younger age groups. However, the rates for TLR and ST were not significantly different across the investigated age groups. PF-SES are safe and effective in octogenarians.

Aktuelle Entwicklungen in der Telemedizin

Sie war mit vielen Erwartungen und Hoffnungen in der Kardiologie verbunden, und sie sollte die Versorgung von Herzinsuffizienzpatienten durch eine individualisierte Überwachung kostengünstig verbessern – doch wo steht sie heute, die Telemedizin für die Versorgung der Herzinsuffizienzpatienten, und welche ihrer anfangs hochgesteckten Erwartungen wurden bislang eingelöst? Diese Fragen gewinnen angesichts von neueren klinischen Studien zum Nutzen der Telemedizin bei Herzinsuffizienzpatienten wieder an Bedeutung. Um den Stellenwert der Telemedizin in den zukünftigen Versorgungsstrukturen des Gesundheitssektors abschätzen zu können, müssen über eine systematische Untersuchung zur klinischen Effektivität telemedizinischer Überwachung hinaus die Perspektiven einer sinnvollen Anwendung von modernen Informationsund Kommunikationstechniken zum Wohl der herzinsuffizienten Patienten in den Blick genommen werden. Das erklärte Ziel von Telemonitoring in der Kardiologie ist u. a. die frühzeitige Erfassung objektiver kardialer Dekompensationszeichen bei subjektiv noch nicht wesentlich beeinträchtigtem Allgemeinzustand, um eine drohende Verschlechterung der Symptomatik durch entsprechende therapeutische Interventionen rechtzeitig verhindern zu können. Trotz unbestreitbarer Erfolge in der Diagnosestellung und Behandlung bleibt die Herzinsuffizienz aufgrund ihrer hohen Prävalenz und ihrer beachtlichen Letalität weiterhin eine sowohl medizinisch als auch volkswirtschaftlich bedeutsame Erkrankung. Angesichts des demographischen Wandels mit dem zu erwartenden Anstieg in der Prävalenz der Herzinsuffizienz werden multidisziplinäre, regional verankerte Versorgungsstrukturen zur Vermeidung von ungeplanten Krankenauseinweisungen bei drohender akuter Dekompensation eingefordert [1–3]. Zudem zwingen die hohen Krankheitskosten für leitliniengerechte, ambulante Behandlungsregime und die Finanzierung der häufigen stationären Aufenthalte zur Suche nach Verbesserungspotenzialen in der Versorgungsqualität von herzinsuffizienten Patienten. Besonders in strukturschwachen Regionen mit geringer Arztdichte verspricht die Telemedizin,übereinfrühzeitigesErkennenkardialer Dekompensationszeichen die hohen Rehospitalisierungsund Mortalitätsraten zu senken. Diese Erwartungen gilt es angesichts einer neuen Studienlage auf ihre Praxistauglichkeit hin zu überprüfen. Unter Einsatz moderner Kommunikationstechnologien ermöglicht die Telemedizin ein kontinuierliches Monitoring kritischer Herzfunktionen sowohl in Echtzeit (synchron) als auch mittels apparativ bedingter Verzögerungen (asynchron) über größere Entfernungen hinweg, weshalb der Patient dafür den Arzt nicht mehr zwingend aufsuchen muss. Zu diesem Zweck werden physiologische Daten der Herzfunktion von risikogefährdeten Patienten von einem Sensor zu einer Auswertungsund Überwachungseinheitübermitteltundvoneinem kardiologisch ausgebildeten Arzt befundet und interpretiert [1]. Die Bereitstellung von entscheidungsrelevanten Informationen dient der schnellen Abschätzung einer unmittelbaren BehandlungsbedürftigkeitundmündetindieFrageder einzuschlagenden Therapiestrategie bei drohender Dekompensation, etwa einer

Propensity score matched all comers population treated with ultra‐thin strut bare metal and sirolimus‐probucol coated drug‐eluting stents of identical stent architecture

The objective of this study was to compare the safety and efficacy of a polymer‐free sirolimus coated, ultrathin strut drug eluting stent (PF‐SES) to its uncoated bare‐metal stent (BMS) platform of identical stent architecture.

Prophylactic ImpellaTM Pump Support in High Risk Percutaneous Coronary Interventions of the Left Main with normal LV Function

In patients with complex coronary anatomy, coronary artery bypass grafting has been the recommended revascularization strategy; however, due to their comorbidities many of these patients have a high operative mortality. Percutaneous coronary intervention (PCI) may then be a viable alternative for these patients with high-risk features. Prophylactic partial hemodynamic support with a micro axial percutaneous left ventricular assist device (ImpellaTM) during PCI might be beneficial in these patients. The ImpellaTM 2.5 blood pump has been shown to be safe and effective in elective and urgent high-risk PCI patients by reducing peri-and post-procedural adverse events. Here, we present several cases of ImpellaTM 2.5 guided high-risk coronary intervention of unprotected left main. The hemodynamic support enabled preserving the mean arterial pressure (MAP) in all cases during repeated coronary manipulations and could be removed due to stable hemodynamic condition of the patients immediately after completion of the intervention. No site insertion or other complications occurred. Further studies are necessary to determine whether these observations can be replicated in a larger cohort.

Kardiovaskuläres Risiko unter Androgendeprivationstherapie zur Behandlung des hormonabhängigen Prostatakarzinoms@@@Cardiovascular risk of androgen deprivation therapy for treatment of hormone-dependent prostate cancer: Unterschiede zwischen GnRH-Antagonisten gegenüber GnRH-Agonisten@@@Differences between GnRH antagonists and GnRH agonists

ZusammenfassungAus mehreren Studien geht hervor, dass das Absenken der Testosteronspiegel bei Patienten mit Prostatakarzinom im Rahmen einer Androgendeprivationstherapie (ADT) mit einem erhöhten Risiko für das Auftreten kardiovaskulärer Ereignisse einhergehen kann, was besonders beim Einsatz von GnRH („gonadotropin-releasing hormone“)-Agonisten aufgefallen ist. Eine ADT mit GnRH-Antagonisten muss jedoch in diesem Zusammenhang aufgrund ihres anderen Wirkmechanismus separat betrachtet werden. In dieser Übersichtsarbeit werden Ursachen für das Auftreten kardiovaskulärer Ereignisse unter ADT diskutiert, die Unterschiede zwischen GnRH-Agonisten und GnRH-Antagonisten im Hinblick auf ihren Wirkmechanismus erläutert, relevante Studien präsentiert und praktische Empfehlungen für den Arzt abgeleitet. Dazu wurde eine Literaturrecherche zu Veröffentlichungen im Zeitraum von 2005 bis September 2015 durchgeführt. Diese ergab, dass Patienten mit Prostatakarzinom unter GnRH-Antagonisten ein geringeres kardiovaskuläres Risiko aufwiesen als Patienten, die mit GnRH-Agonisten behandelt wurden. Dies galt insbesondere für Patienten, die kardiovaskulär erkrankt waren. Die unterschiedlichen Wirkmechanismen beider Substanzklassen liefern erste Erklärungen für das geringere kardiovaskuläre Risiko unter GnRH-Antagonisten. Patienten mit kardiovaskulärer Vorerkrankung oder dem Risiko für ein kardiovaskuläres Ereignis sollten vorzugsweise mit einem GnRH-Antagonisten behandelt werden.AbstractBackgroundSeveral studies have indicated that reduction of testosterone levels in patients with prostate cancer undergoing androgen deprivation therapy (ADT) with gonadotropin-releasing hormone (GnRH) agonists can be associated with an increased risk of cardiovascular events. The GnRH antagonists have a different mode of action compared with GnRH agonists and may be preferred in ADT for patients with cardiovascular disease.ObjectiveThis review article discusses potential mechanisms underlying the development of cardiovascular events associated with ADT when using GnRH agonists and explains the differences in mode of action between GnRH agonists and GnRH antagonists. Additionally, relevant studies are presented and practical recommendations for the clinical practice are provided.Material and methodsA literature search was performed. Full publications and abstracts published in the last 10 years up to September 2015 were considered to be eligible.ResultsThe GnRH antagonists were associated with a decreased risk of cardiovascular events compared with GnRH agonists in prostate cancer patients undergoing ADT and particularly in patients with cardiovascular risk factors or a history of cardiovascular disease. This decrease may be due to the different mode of action of GnRH antagonists compared with GnRH agonists.ConclusionProstate cancer patients with either cardiovascular disease or an increased risk of experiencing a cardiovascular event undergoing ADT should be preferentially treated with GnRH antagonists.