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Objectives This study sought to investigate predictors of procedural success and clinical outcomes in patients with tricuspid regurgitation (TR) at increased surgical risk undergoing transcatheter tricuspid valve edge-to-edge repair (TTVR). Background Recent data suggest TTVR using the edge-to-edge repair technique in patients at high surgical risk is feasible and improves functional status at short-term follow-up. Methods TTVR was carried out in 117 patients with symptomatic TR (median age 79.0 years [interquartile range (IQR): 75.5 to 83.0 years], EuroSCORE II 6.3% [IQR: 4.1% to 10.8%], STS mortality score 5.3% [IQR: 2.9% to 7.1%]) at 2 centers in Germany between March 2016 and November 2017. Seventy-four patients had concomitant severe mitral regurgitation and underwent transcatheter edge-to-edge repair of both valves. Results During TTVR, 185 and 34 clips were implanted at the anteroseptal and posteroseptal commissures, respectively. Procedural success (TR reduction ≥1) was achieved in 81% of patients. Median TR effective regurgitant orifice area was reduced from 0.5 to 0.2 cm2. After a median follow-up of 184 days (IQR: 106 to 363 days), 24 patients died and 21 patients were readmitted for heart failure. TTVR procedural success independently predicted the time free of death and admission for heart failure (hazard ratio: 0.20 [95% confidence interval: 0.08 to 0.48]; p Conclusions Successful TR reduction by TTVR serves as a predictor for reduced mortality and heart failure hospitalization. TR coaptation gap and jet location may assist in decision making whether a patient is anatomically suited for TTVR.

Inappropriate activation of the renin angiotensin system (RAS) is a key contributor to the pathogenesis of essential hypertension. During RAS activation, infiltration of immune cells into the kidney exacerbates hypertension and renal injury. However, the mechanisms underpinning the accumulation of mononuclear cells in the kidney after RAS stimulation remain unclear. C-C motif chemokine 5 (CCL5) drives recruitment of macrophages and T lymphocytes into injured tissues, and we have found that RAS activation induces CCL5 expression in the kidney during the pathogenesis of hypertension and renal fibrosis. We therefore evaluated the contribution of CCL5 to renal damage and fibrosis in hypertensive and normotensive models of RAS stimulation. Surprisingly, during angiotensin II-induced hypertension, CCL5-deficient (knockout, KO) mice exhibited markedly augmented kidney damage, macrophage infiltration, and expression of proinflammatory macrophage cytokines compared with wild-type controls. When subjected to the normotensive unilateral ureteral obstruction model of endogenous RAS activation, CCL5 KO mice similarly developed more severe renal fibrosis and greater accumulation of macrophages in the kidney, congruent with enhanced renal expression of the macrophage chemokine CCL2. In turn, pharmacologic inhibition of CCL2 abrogated the differences between CCL5 KO and wild-type mice in kidney fibrosis and macrophage infiltration after unilateral ureteral obstruction. These data indicate that CCL5 paradoxically limits macrophage accumulation in the injured kidney during RAS activation by constraining the proinflammatory actions of CCL2.

Inappropriate activation of the renin-angiotensin system (RAS) contributes to many CKDs. However, the role of the RAS in modulating AKI requires elucidation, particularly because stimulating type 1 angiotensin II (AT1) receptors in the kidney or circulating inflammatory cells can have opposing effects on the generation of inflammatory mediators that underpin the pathogenesis of AKI. For example, TNF-α is a fundamental driver of cisplatin nephrotoxicity, and generation of TNF-α is suppressed or enhanced by AT1 receptor signaling in T lymphocytes or the distal nephron, respectively. In this study, cell tracking experiments with CD4-Cre mT/mG reporter mice revealed robust infiltration of T lymphocytes into the kidney after cisplatin injection. Notably, knockout of AT1 receptors on T lymphocytes exacerbated the severity of cisplatin-induced AKI and enhanced the cisplatin-induced increase in TNF-α levels locally within the kidney and in the systemic circulation. In contrast, knockout of AT1 receptors on kidney epithelial cells ameliorated the severity of AKI and suppressed local and systemic TNF-α production induced by cisplatin. Finally, disrupting TNF-α production specifically within the renal tubular epithelium attenuated the AKI and the increase in circulating TNF-α levels induced by cisplatin. These results illustrate discrepant tissue–specific effects of RAS stimulation on cisplatin nephrotoxicity and raise the concern that inflammatory mediators produced by renal parenchymal cells may influence the function of remote organs by altering systemic cytokine levels. Our findings suggest selective inhibition of AT1 receptors within the nephron as a promising intervention for protecting patients from cisplatin-induced nephrotoxicity.

Pulmonary arterial hypertension (PAH) is a severe, progressive and fatal disease. The creation of an interatrial right-to-left shunt in patients with PAH may enhance systemic ventricular output at the expense of desaturation. However, creating sustainable restricted interatrial communication is challenging. We describe the successful use of an atrial flow regulator, a novel implantable atrial communication device, in a 54-year-old female with severe irreversible PAH.

BACKGROUND: Electrical devices generate electromagnetic fields that may interfere with pacemakers. Media players cause telemetry interference with pacemakers, but it is not known whether they cause direct interference with pacemakers. The purpose of this study was to examine the interaction between pacemakers and 3 different media players. METHODS: In this prospective, randomized study, 54 patients with dual chamber pacemakers who were in sinus rhythm underwent baseline observation, followed by observation under telemetry communication. These patients were then randomly evaluated with 3 media players (iPod 3G, iPod Photo, and iPod Touch Apple, Cupertino, CA) with and without telemetry communication for 1 minute each. Patients were monitored for pacemaker malfunction using a single‐channel ECG during exposure to media players. The pacemaker was interrogated after each exposure and an interrogation report was printed for evaluation. Pacemaker interference was categorized as type I, II, or III. Types I and II interference described telemetry interference and type III interference was defined as any direct interference with pacemaker function or programmed parameters. RESULTS: A total of 54 patients (29 men and 25 women; mean age 77.2 ± 9.3 y) were evaluated. In total, of the 162 tests (for telemetry interference) 36.4% were positive (Type I and II). Type III interference was also evaluated in 162 tests and none showed any evidence of direct interference. CONCLUSION: Media players cause telemetry interference with pacemakers, but they do not directly interfere with pacemaker function. Copyright © 2009 Wiley Periodicals, Inc.

Porphyrias are a group of inherited disorders affecting enzymes in the heme biosynthesis pathway, leading to overproduction and/or accumulation of porphyrin or its precursors. Porphyrias have been associated with autonomic dysfunction, which in turn can develop atrial fibrillation (AF). The purpose of this study was to characterize the prevalence of AF and atrial flutter (AFl) in patients with porphyrias. A single-center retrospective cohort study was designed using data from chart reviews of patients who were admitted to the hospital from January 2000 to June 2008. Fifty-six distinct cases were found with a discharge diagnosis of porphyria including all its subtypes. From the same database, age- and gender-matched controls were identified using computer-generated random numbers. We selected 1 age- and gender-matched control for each case. Electrocardiograms and echocardiograms were reviewed by 2 independent reviewers. Only patients with available 12-lead electrocardiograms that showed AF/AFl were labeled with that diagnosis. All patients with a diagnosis of porphyria were included in the study irrespective of their age. Seven of 56 patients with porphyria met inclusion criteria, yielding a prevalence of AF/AFl of 12.5%. This association was significant (p = 0.028, relative risk 7.45, 95% confidence interval 1.01 to 66.14) compared with the age- and gender-matched control group (2%). In conclusion, our observations suggest that porphyria may be significantly associated with AF/AFl.

Intra-operative hypotension has been reported in cardiac resynchronization therapy defibrillator (CRT-D) clinical trials but this phenomenon is not well characterized. The purpose of this study was to understand the frequency and determinants of intra-operative hypotension in patients undergoing defibrillator implantations.We retrospectively reviewed clinical data of all CRT-D implantations over a 21-month period. We compared a randomly selected contemporaneous group undergoing implantable cardiac defibrillator (ICD) implantations as a reference group. Procedure protocol involved intra-arterial blood pressure monitoring throughout the case. Lidocaine (1%) was routinely used along with propofol for sedation in all patients. Procedure time was defined as the time from initial administration of lidocaine for arterial line access, to completion of defibrillator pocket closure. Cumulative dose of propofol was calculated in each patient. Hypotension was defined as a fall in the systolic blood pressure ofor=30% from baseline or a systolic blood pressure ofor=80 mm Hg for3 min. CRT-D and ICD patients were divided into hypotensive and non-hypotensive subsets.The incidence of hypotension in the CRT-D group (N = 100) was 56%, as compared to 40% in the ICD group (N = 97). The mean duration of procedure in the CRT-D group was 114 +/- 95 min in the hypotensive subset versus 69 +/- 31.9 min in the non-hypotensive subset (p = 0.0015). The mean NYHA class in the hypotensive subset of the CRT-D group was 2.85 +/- 1.2 vs 2.2 +/- 1.5 in the non-hypotensive subset (p = 0.0179). Cumulative dose of propofol in the hypotensive subset of the CRT-D group was 386 +/- 22 mg, while that in the non hypotensive subset was 238.3 +/- 17 mg (p0.0001). Creatinine clearance in the hypotensive subset of the CRT-D group was 63.8 +/- 12.8 ml/min, while that in the non-hypotensive subset was 78.7 +/- 23.5 ml/min (p = 0.003). Patients in the CRT-D group who developed hypotension had a lower left ventricular ejection fraction of 21.1 +/- 10.2% versus 29 +/- 14.8% in the non-hypotensive subset (p = 0.0035).Hypotension is a common occurrence during defibrillator implantation under conscious sedation. Risk factors for significant hypotension include: higher NYHA class, lower left ventricular ejection fraction, lower creatinine clearance, higher doses of propofol and longer procedure times.

We report three cases of an unusual form of "reel syndrome" characterized by isolated, reeling dislodgement of a single lead in patients with dual-chamber or biventricular devices. One of these patients presented with worsening heart failure due to loss of left ventricular pacing and the others were detected incidentally during scheduled device checks. We suspect that a ratchet mechanism was probably responsible for this and that this type of dislodgement is not a twiddler variant. We propose a simple solution for prevention.

Hypotension as a procedural complication during cardiac resynchronization therapy (CRT) implantation was reported in the initial randomized clinical trials. However, this phenomenon is not well characterized. We reviewed our CRT implantation experience to better understand this issue. There were 105 patients who underwent left ventricular lead implantation for CRT. Four patients had marked hypotension (systolic blood pressure < or = 50 mmHg) during the procedure. All had a history of hypertension and diabetes mellitus and were pacemaker dependent. Two had normal renal function, one had moderate renal insufficiency, and one was on dialysis. Three patients had ischemic cardiomyopathy. All had left ventricular ejection fraction < or =20% and were in New York Heart Association class III. Propofol and midazolam were used for sedation as standard protocol. Two patients had sudden hypotension when the coronary sinus was being cannulated, and two patients experienced sudden hypotension during left ventricular pacing. Cardiac tamponade as a possible cause was ruled out by echocardiography. We discuss possible mechanisms of sudden hemodynamic collapse during CRT implantation.

a i ntroduction lectromagnetic interference (EMI) is generally defined as nterference of normal device function caused by an exterally generated signal. Ever increasing use of electronic evices has led to an increase in sources of electromagnetic adiation. This is a cause of concern in patients with imlanted pacemakers. Numerous environmental sources of lectromagnetic radiation cause EMI. Current pacemakrs have built-in bandpass and feedthrough filters that diinish the probability of EMI. However, EMI still occurs espite these technologic improvements. Cellular telehones and antitheft surveillance systems are some new ources of interference. The iPod (Apple Computer Inc., Cupertino, CA, USA) is widely used brand of portable media player for personal ntertainment that has become quite ubiquitous. It is estiated that since its introduction in 2001, more than 100 illion iPods will have been sold by 2007. Furthermore, Pods may soon be used in the hospital setting as a teaching r monitoring tool. We report a case of pacemaker interfernce caused by an iPod.

Upper limit of vulnerability (ULV) testing using T-wave scanning shocks at multiple coupling intervals correlates well with defibrillation threshold (DFT), but remains underutilized in clinical practice. We measured DFT and ULV at a single coupling interval (SCI), with the aim to identify adequate safety margin at a coupling interval that correlates best with DFT.Consecutive patients undergoing implantable cardioverter defibrillator implantation underwent simultaneous SCI-ULV and DFT assessment. Following a drive train of 400 ms, a T-wave-coupled shock was delivered. To minimize shocks, patients were randomized to programmed shock at 20 ms before peak (Group I), at peak (Group II), or 20 ms after peak (Group III) of T wave. An initial T-wave test shock at 9 J was followed by ±2 J shocks, until SCI-ULV was ascertained. Device rescue shocks were programmed at test shock +2 J and +4 J shocks followed by external rescue shock.There were 200 patients: 66 patients in Group I, 67 patients each in Groups II and III; mean age was 68.9 ± 12.4 years; 75% of patients men, 66% with ischemic heart disease and mean ejection fraction of 27.1 ± 7.1%. Overall, the mean number of ventricular fibrillation induction was 1.39 ± 0.8, mean SCI-ULV energy was 7.97 ± 3.39 J, and mean DFT was 8.68 ± 3.19 J. The correlation between SCI-ULV and DFT improved from Group I to Group III and was best in Group III (r(2) = 0.689). There were no major adverse events.SCI-ULV measured 20 ms after the peak of the T wave correlates well with DFT for assessment of adequate safety margin.

Limitations imposed by the coronary sinus venous anatomy triggered the transseptal approach for endocardial LV lead placement. The alignment of the interatrial septum (IAS) and its neighborhood anatomy does not favor transseptal puncture from the pre-pectoral area. Locating and advancing a pre-pectoral LV lead delivery catheter (PDC) through an opening created in the IAS via femoral transseptal puncture (FTP) is time consuming and technically difficult. We describe a method where the PDC is snare coupled to the femoral transseptal apparatus (FTA). When the FTA is advanced into the left atrium (LA) the coupled PDC follows. The catheter of a 25-mm loop snare kit is replaced with the PDC (SelectSite®). The snare loop is positioned in the right common iliac vein from the pre-pectoral access. The PDC is coupled to the FTA by advancing the transseptal apparatus through the open snare loop. After conventional FTP, the FTA is withdrawn back into the right atrium (RA) over an extra support wire positioned in the LA. The PDC with open snare loop is pulled over the FTA up to the RA. The PDC is advanced to close the snare loop on the extra support wire immediately distal to the tip of the dilator close to the puncture site. The PDC is deflected to align with the FTA. The snare coupled catheters are gently advanced across the IAS into the LA. The PDC is released from the FTA by advancing the snare and opening the loop; the snare is then removed from the PDC. The PDC is deflected and advanced into the left ventricle (LV). After positioning the 4.1 Fr lumen less LV lead, the PDC is sliced and removed. The PDC snare coupled to the FTA was advanced into the LA in all five patients, however, access was lost during catheter manipulation in the one right-sided case. Endocardial LV lead was successfully positioned in all five patients. Snare coupling the pre-pectoral SelectSite® catheter to the FTA is technically simple, reliable and a safe method for transseptal endocardial LV lead placement for left pre-pectoral implantation.

Contemporary implantable heart rhythm devices communicate multiple complex data simultaneously using radiofrequency telemetry. Interference in communication can expose them to the risk of potential corruption, leading to adverse clinical consequences.We studied the characteristics of interference with uplink (real time intracardiac electrograms, marker channel, and stored histograms) and downlink (attempt to program a change in the lower rate limit, the pacing mode, and the ventricular lead configuration) data transmission between the wand and the pacemaker caused by digital media players (iPods--Photo and 3G) in 50 patients. We also measured and characterized worst-case magnetic field emissions (MFE) from the wand (or=0.4 microT), pacemaker (or=0.004 microT), and iPod (or=0.05 microT) during telemetry to understand the modulation techniques and safety protocols employed during data transmission. Telemetry interference (TI) manifested as high-frequency spikes (24.4%), blanking (17.7%) and interruption (22.2%), or delay (17.6%) in transmission with warning on programmer's screen. TI occurred in 25.6% of patients when the iPod was "on" and in 13% even with the iPod turned "off." There were no inaccuracies in downlinked data when the downlink communication was successful. Wanded telemetry utilizes low-frequency (30-300 kHz) radiowaves and simple digital modulation techniques at relatively slow rates for "sequential" data transmission protected by a continuous "handshake." Emissions from iPods in that range interrupt the telemetry link but are too weak to cause pacemaker malfunction through corruption of vital data.Low-power MFE from iPods can produce interference with establishment and maintenance of a telemetry link and can cause TI with transmission of real time data, but because of continuous check protocols, do not corrupt the stored and vital downlink data.

Concurrent abuse of alcohol and cocaine results in the formation of cocaethylene, a powerful cocaine metabolite. Cocaethylene potentiates the direct cardiotoxic and indirect neurotoxic effects of cocaine or alcohol alone.A 44-year-old female with history of cocaine and alcohol abuse presented with massive stroke in the emergency department. CT scan revealed extensive left internal carotid artery dissection extending into the left middle and anterior cerebral arteries resulting in a massive left hemispheric infarct, requiring urgent decompressive craniectomy. The patient had a stormy hospital course with multiple episodes of torsades de pointes in the first 4 days requiring aggressive management. She survived all events and was discharged to a nursing home with residual right hemiplegia and aphasia.The combination of ethanol and cocaine has been associated with a significant increase in the incidence of neurological and cardiac emergencies including cerebral infarction, intracranial hemorrhage, myocardial infarction, cardiomyopathy, and cardiac arrhythmias. The alteration of cocaine pharmacokinetics and the formation of cocaethylene have been implicated, at least partially, in the increased toxicity of this drug combination.

The implantable loop recorder is a useful diagnostic tool for intermittent cardiovascular symptoms because it can automatically record arrhythmias as well as a patient-triggered ECG. Media players have been shown to cause telemetry interference with pacemakers. Telemetry interference may be important in patients with implantable loop recorders because capturing a patient-triggered ECG requires a telemetry link between a hand-held activator and the implanted device. The purpose of this study was to determine if a media player causes interference with implantable loop recorders. Fourteen patients with implantable loop recorders underwent evaluation for interference with a 15 GB third generation iPodTM (Apple, Inc.) media player. All patients had the Reveal PlusTM (Medtronic, Inc.) implantable loop recorder. We tested for telemetry interference on the programmer by first establishing a telemetry link with the loop recorder and then, the media player was placed next to it, first turned off and then, on. We evaluated for telemetry interference between the activator and the implanted device by placing the activator over the device (normal use) and the media player next to it, first turned off and then, on. We made 5 attempts to capture a patient-triggered ECG by depressing the activator switch 5 times while the media player was off or on. Telemetry interference on the programmer screen, consisting of either high frequency spikes or blanking of the ECG channel was seen in all patients. Telemetry interference with the activator resulted in failure to capture an event in 7 patients. In one of these patients, a green indicator light on the activator suggested that a patient-triggered event was captured, but loop recorder interrogation did not show a captured event. In the remaining 7 patients, an event was captured and appropriately recognized by the device at least 1 out of 5 times. A media player playing in close proximity to an implanted loop recorder may interfere with capture of a patient-triggered event. Patients should be advised to keep media players away from their implanted loop reorder.

Cor triatriatum sinister is a rare condition caused by a membrane in the left atrium, resulting in left ventricular inflow obstruction. This developmental anomaly is usually diagnosed in childhood. However, a rare presentation during adulthood is observed when the membrane is incomplete. Surgical excision of the membrane is the first line of treatment. We present a 51-year-old woman who underwent successful transcatheter balloon dilation with complete loss of the membrane waist and hemodynamic and symptomatic improvement.

A 21-year-old pregnant patient was admitted for the management of bilateral pulmonary emboli. A transthoracic echocardiogram was performed to evaluate cardiac status, which revealed the presence of a membrane in the left atrium, and a bicuspid aortic valve. The finding was confirmed by transesophageal echocardiography. The patient was treated with low molecular weight heparin. Cor triatriatum sinister, which refers to the presence of a band or membrane in the left atrium is very rare, and Figure 2. Transthoracic echocardiogram shows a bicuspid aortic valve (two cusps are shown with arrows).