The Importance of Mitral Valve Prolapse Doming Volume in the Assessment of Left Ventricular Stroke Volume with Cardiac MRI.

There remains a debate whether the ventricular volume within prolapsing mitral valve (MV) leaflets should be included in the left ventricular (LV) end-systolic volume, and therefore factored in LV stroke volume (SV), in cardiac magnetic resonance (CMR) assessments. This study aims to compare LV volumes during end-systolic phases, with and without the inclusion of the volume of blood on the left atrial aspect of the atrioventricular groove but still within the MV prolapsing leaflets, against the reference LV SV by four-dimensional flow (4DF). A total of 15 patients with MV prolapse (MVP) were retrospectively enrolled in this study. We compared LV SV with (LV SVMVP) and without (LV SVstandard) MVP left ventricular doming volume, using 4D flow (LV SV4DF) as the reference value. Significant differences were observed when comparing LV SVstandard and LV SVMVP (p < 0.001), and between LV SVstandard and LV SV4DF (p = 0.02). The Intraclass Correlation Coefficient (ICC) test demonstrated good repeatability between LV SVMVP and LV SV4DF (ICC = 0.86, p < 0.001) but only moderate repeatability between LV SVstandard and LV SV4DF (ICC = 0.75, p < 0.01). Calculating LV SV by including the MVP left ventricular doming volume has a higher consistency with LV SV derived from the 4DF assessment. In conclusion, LV SV short-axis cine assessment incorporating MVP dooming volume can significantly improve the precision of LV SV assessment compared to the reference 4DF method. Hence, in cases with bi-leaflet MVP, we recommend factoring in MVP dooming into the left ventricular end-systolic volume to improve the accuracy and precision of quantifying mitral regurgitation.

An updated systematic review on heart failure treatments for patients with renal impairment: the tide is not turning.

Advanced chronic kidney disease (CKD) frequently aggravates heart failure (HF). However, these patients have inherently been excluded from most HF trials. We aim to provide updated estimates of the representation of patients with advanced CKD and the provision of baseline renal function indices in HF trials with a focused interest on the landmark trials. Updated systematic review was performed from the inception of MEDLINE to 31 December 2019 to identify all chronic HF randomized trials published in the three major cardiology and medical journals, respectively, which included mortality endpoint. The included studies were analysed based on the representativeness of the advanced CKD population and the reporting of baseline renal function. A total of 187 eligible randomized trials with 322,374 participants were included in our analysis. One hundred and six trials (56.7%) had exclusion criteria related to renal function, which remained a continuing trend-55.1% (27/49) from inception-2000, 53.4% (39/73) from 2001-2010 and 61.5% (40/65) from 2011 (P = 0.64). The exclusion criteria, however, have become less restrictive. There was a temporal improvement in the likelihood of HF trials in providing baseline renal function indices (28.6% from inception-2000 versus 53.4% from 2001-2010 and 83.1% from 2011, P < 0.001). Concordant findings were observed in the landmark trials. Patients with advanced CKD remain underrepresented in HF trials in the contemporary era, even though the exclusion criteria have become less restrictive, and the quality of renal function monitoring has improved. The continued underrepresentation of patients with advanced CKD in HF trials merits measured broadening of eligibility in further trial studies.

Long-Term Impact of Body Mass Index on Survival of Patients Undergoing Cardiac Resynchronization Therapy: A Multi-Centre Study.

Obesity is a risk factor for heart failure (HF), but its presence among HF patients may be associated with favorable outcomes. We investigated the long-term outcomes across different body mass index (BMI) groups, after cardiac resynchronization therapy (CRT), and whether defibrillator back-up (CRT-D) confers survival benefit. One thousand two-hundred seventy-seven (1,277) consecutive patients (mean age: 67.0 ± 12.7 years, 44.1% women, and mean BMI: 28.3 ± 5.6 Kg/m2) who underwent CRT implantation in 5 centers between 2000-2014 were followed-up for a median period of 4.9 years (IQR 2.4 to 7.5). More than 10% of patients had follow-up for ≥10 years. Patients were classified according to BMI as normal: <25.0 Kg/m2, overweight: 25.0 to 29.9 Kg/m2 and obese: ≥30.0 Kg/m2. 364 patients had normal weight, 494 were overweight and 419 were obese. CRT-Ds were implanted in >75% of patients, but were used less frequently in obese individuals. The composite endpoint of all-cause mortality or cardiac transplant/left ventricular assist device (LVAD) occurred in 50.9% of patients. At 10-year follow-up, less than a quarter of patients in the lowest and highest BMI categories were still alive and free from heart transplant/LVAD. After adjustment BMI of 25 to 29.9 Kg/m2 (HR = 0.73 [95%CI 0.56 to 0.96], p = 0.023) and use of CRT-D (HR = 0.74 [95% CI 0.55 to 0.98], p = 0.039) were independent predictors of survival free from LVAD/heart transplant. BMI of 25 to 29.9 Kg/m2 at the time of implant was independently associated with favourable long-term 10-year survival. Use of CRT-D was associated with improved survival irrespective of BMI class.

Time trends in sudden cardiac death risk in heart failure patients with cardiac resynchronization therapy: a systematic review.

AIMS: While data from randomized trials suggest a declining incidence of sudden cardiac death (SCD) among heart failure patients, the extent to which such a trend is present among patients with cardiac resynchronization therapy (CRT) has not been evaluated. We therefore assessed changes in SCD incidence, and associated factors, in CRT recipients over the last 20 years. METHODS AND RESULTS: Literature search from inception to 30 April 2018 for observational and randomized studies involving CRT patients, with or without defibrillator, providing specific cause-of-death data. Sudden cardiac death was the primary endpoint. For each study, rate of SCD per 1000 patient-years of follow-up was calculated. Trend line graphs were subsequently constructed to assess change in SCD rates over time, which were further analysed by device type, patient characteristics, and medical therapy. Fifty-three studies, comprising 22 351 patients with 60 879 patient-years of follow-up and a total of 585 SCD, were included. There was a gradual decrease in SCD rates since the early 2000s in both randomized and observational studies, with rates falling more than four-fold. The rate of decline in SCD was steeper than that of all-cause mortality, and accordingly, the proportion of deaths which were due to SCD declined over the years. The magnitude of absolute decline in SCD was more prominent among CRT-pacemaker (CRT-P) patients compared to those receiving CRT-defibrillator (CRT-D), with the difference in SCD rates between CRT-P and CRT-D decreasing considerably over time. There was a progressive increase in age, use of beta-blockers, and left ventricular ejection fraction, and conversely, a decrease in QRS duration and antiarrhythmic drug use. CONCLUSION: Sudden cardiac death rates have progressively declined in the CRT heart failure population over time, with the difference between CRT-D vs. CRT-P recipients narrowing considerably.

Very long-term survival and late sudden cardiac death in cardiac resynchronization therapy patients.

AIMS: The very long-term outcome of patients who survive the first few years after receiving cardiac resynchronization therapy (CRT) has not been well described thus far. We aimed to provide long-term outcomes, especially with regard to the occurrence of sudden cardiac death (SCD), in CRT patients without (CRT-P) and with defibrillator (CRT-D). METHODS AND RESULTS: A total of 1775 patients, with ischaemic or non-ischaemic dilated cardiomyopathy, who were alive 5 years after CRT implantation, were enrolled in this multicentre European observational cohort study. Overall long-term mortality rates and specific causes of death were assessed, with a focus on late SCD. Over a mean follow-up of 30 months (interquartile range 10-42 months) beyond the first 5 years, we observed 473 deaths. The annual age-standardized mortality rates of CRT-D and CRT-P patients were 40.4 [95% confidence interval (CI) 35.3-45.5] and 97.2 (95% CI 85.5-109.9) per 1000 patient-years, respectively. The adjusted hazard ratio (HR) for all-cause mortality was 0.99 (95% CI 0.79-1.22). Twenty-nine patients in total died of late SCD (14 with CRT-P, 15 with CRT-D), corresponding to 6.1% of all causes of death in both device groups. Specific annual SCD rates were 8.5 and 5.8 per 1000 patient-years in CRT-P and CRT-D patients, respectively, with no significant difference between groups (adjusted HR 1.0, 95% CI 0.45-2.44). Death due to progressive heart failure represented the principal cause of death (42.8% in CRT-P patients and 52.6% among CRT-D recipients), whereas approximately one-third of deaths in both device groups were due to non-cardiovascular death. CONCLUSION: In this first description of very long-term outcomes among CRT recipients, progressive heart failure death still represented the most frequent cause of death in patients surviving the first 5 years after CRT implant. In contrast, SCD represents a very low proportion of late mortality irrespective of the presence of a defibrillator.

Catastrophic antiphospholipid syndrome causing ST-segment elevation myocardial infarction with non-obstructive coronary arteries.

A 51-year-old woman with known primary antiphospholipid syndrome presented with a 4-day history of chest and abdominal pain, inferior ST-segment elevation on a 12-lead ECG and a subtherapeutic international normalised ratio. In view of a significantly raised high-sensitivity troponin I assay, inferior wall hypokinesis on transthoracic echocardiography and despite unobstructed epicardial vessels on emergency coronary angiography, a diagnosis of myocardial infarction was made. Furthermore, the patient also developed both bilateral adrenal haemorrhages leading to acute adrenal insufficiency and microvascular thrombotic renal disease concurrently. The patient therefore fulfilled the diagnostic criteria for catastrophic antiphospholipid syndrome presenting with cardiac, endocrine and renal involvement. Early diagnosis permitted appropriate treatment with anticoagulation, dual antiplatelet therapy, secondary prevention and corticosteroid replacement therapy and led to a full recovery. This case highlights first the importance of adequate anticoagulation in antiphospholipid syndrome and, second, the potentially fatal, multiorgan complication of failure to do so.

Device complications with addition of defibrillation to cardiac resynchronisation therapy for primary prevention.

OBJECTIVE: In patients indicated for cardiac resynchronisation therapy (CRT), the choice between a CRT-pacemaker (CRT-P) versus defibrillator (CRT-D) remains controversial and indications in this setting have not been well delineated. Apart from inappropriate therapies, which are inherent to the presence of a defibrillator, whether adding defibrillator to CRT in the primary prevention setting impacts risk of other acute and late device-related complications has not been well studied and may bear relevance for device selection. METHODS: Observational multicentre European cohort study of 3008 consecutive patients with ischaemic or non-ischaemic dilated cardiomyopathy and no history of sustained ventricular arrhythmias, undergoing CRT implantation with (CRT-D, n=1785) or without (CRT-P, n=1223) defibrillator. Using propensity score and competing risk analyses, we assessed the risk of significant device-related complications requiring surgical reintervention. Inappropriate shocks were not considered except those due to lead malfunction requiring lead revision. RESULTS: Acute complications occurred in 148 patients (4.9%), without significant difference between groups, even after considering potential confounders (OR=1.20, 95% CI 0.72 to 2.00, p=0.47). During a mean follow-up of 41.4±29 months, late complications occurred in 475 patients, giving an annual incidence rate of 26 (95% CI 9 to 43) and 15 (95% CI 6 to 24) per 1000 patient-years in CRT-D and CRT-P patients, respectively. CRT-D was independently associated with increased occurrence of late complications (HR=1.68, 95% CI 1.27 to 2.23, p=0.001). In particular, when compared with CRT-P, CRT-D was associated with an increased risk of device-related infection (HR 2.10, 95% CI 1.18 to 3.45, p=0.004). Acute complications did not predict overall late complications, but predicted device-related infection (HR 2.85, 95% CI 1.71 to 4.56, p<0.001). CONCLUSIONS: Compared with CRT-P, CRT-D is associated with a similar risk of periprocedural complications but increased risk of long-term complications, mainly infection. This needs to be considered in the decision of implanting CRT with or without a defibrillator.

Cause-of-death analysis in patients with cardiac resynchronization therapy with or without a defibrillator: a systematic review and proportional meta-analysis.

Aims: The additional benefit of a defibrillator in cardiac resynchronization therapy (CRT) patients is a matter of debate. Cause-of-death analysis in a CRT population has been recently proposed as a useful approach to gain insight into this problem. We performed a systematic review and meta-analysis looking at cause of death in studies involving CRT subjects with (CRT-D) or without (CRT-P) a defibrillator. Methods and results: Literature search performed from inception to 31 March 2016 for relevant studies. Proportional and conventional meta-analyses were performed to obtain and compare causes of death in CRT-D vs. CRT-P patients, including sudden cardiac death (SCD), all-cause mortality, heart failure, cardiovascular, and non-cardiovascular mortalities. The systematic review included a total of 44 studies and 18 874 patients (13 248 receiving CRT-D and 5626 receiving CRT-P), representing 48 504 patient-years of follow-up. CRT-D recipients were younger, more often male, had lower NYHA class, less atrial fibrillation, more ischaemic heart disease and were more often on beta-blockers than those receiving CRT-P. There were an additional 42 deaths per 1000 patient-years in the CRT-P group compared with CRT-D (97 ± 9, 95% CI 79-115 vs. 55 ± 5, 95% CI 44-65, respectively), of which 35.7% were due to SCD (20 ± 2, 95% CI 15-24 vs. 5 ± 1, 95% CI 3-6) and the remaining 64.3% due to non-SCD. Of all deaths reported in CRT-D and CRT-P patients, 9.1% and 20.6% were due to SCD, respectively. The extent of SCD in CRT-P patients significantly increased in studies with higher percentage of males, ischaemic cardiomyopathy and NYHA class 3. Conclusion: Overall, compared with CRT-D patients, unadjusted mortality rate was almost two-fold higher in CRT-P recipients, with SCD representing one third of the excess mortality. Rate of SCD was significantly higher in certain subgroups (males, ischaemic cardiomyopathy, NYHA class 3), where a CRT-D may be of more pronounced benefit. This deserves further focused investigation.

Patients upgraded to cardiac resynchronization therapy due to pacing-induced cardiomyopathy are at low risk of life-threatening ventricular arrhythmias: a long-term cause-of-death analysis.

Aims: Upgrade to cardiac resynchronization therapy (CRT) should be offered to patients who have developed pacing-induced cardiomyopathy with conventional right ventricular pacing. The extent to which these patients would also benefit from defibrillator back-up at the time of CRT upgrade is, however, unknown. Methods and results: Retrospective observational cohort study of 199 patients with pacing-induced cardiomyopathy and no history of sustained ventricular arrhythmia, including 104 upgraded to CRT-Pacemaker (CRT-P) and 95 upgraded to CRT-Defibrillator (CRT-D). The incidence of ventricular arrhythmias and the risk of sudden arrhythmic death obtained through a cause-of-death analysis based on clinical data and necropsy results were assessed and compared between the two groups. During a mean follow-up of 66 ± 24 months, 40 (38.5%) CRT-P patients died: three from primary arrhythmic death, while the remaining died of different causes (especially progressive heart failure), giving an incidence of 6.2 sudden arrhythmic deaths per 1000 patient-years. No episode of sustained VT was observed in the study group. There were no sudden arrhythmic deaths in the CRT-D group during a shorter follow-up, but the small and non-significant difference in all-cause mortality between CRT-Pacemaker (CRT-P) and CRT-D groups was mostly accounted for by an increase in non-sudden death. Women upgraded to CRT were at particularly low risk of all-cause mortality compared with men (HR 0.232, P = 0.048). Conclusion: Our findings suggest that patients who develop pacing-induced cardiomyopathy and are upgraded to CRT may not derive any significant benefit from the addition of the defibrillator in the absence of a history of ventricular arrhythmias.

Dual-site right ventricular pacing in patients undergoing cardiac resynchronization therapy: Results of a multicenter propensity-matched analysis.

BACKGROUND: Dual-site right ventricular pacing (Dual RV) has been proposed as an alternative for patients with heart failure undergoing cardiac resynchronization therapy (CRT) with a failure to deliver a coronary sinus (CS) lead. Only short-term hemodynamic and echocardiographic results of Dual RV are available. We aimed to assess the long-term results of Dual RV and its impact on survival. METHODS: Multicenter retrospective assessment of all CRT implants during a 12-year period. Patients with failed CS lead implantation, treated with Dual RV, were followed and assessed for the primary endpoint of all-cause mortality and/or heart transplant. A control group was obtained from contemporary patients using propensity matching for all available baseline variables. RESULTS: Ninety-three patients were implanted with Dual RV devices and compared with 93 matched controls. During a median of 1,273 days (interquartile range 557-2,218), intention-to-treat analysis showed that all-cause mortality and/or heart transplant was higher in the Dual RV group (adjusted hazard ratio [HR] = 1.66, 95% confidence interval [CI] 1.12-2.47, P = 0.012). As-treated analysis yielded similar results (HR = 1.97, 95% CI 1.31-2.96, P = 0.001). Cardiac device-related infections occurred seven times more frequently in the Dual RV site group (HR = 7.60, 95% CI 1.51-38.33, P = 0.014). Among Dual RV nonresponders, four had their apical leads switched off, five required an epicardial LV lead insertion, a transseptal LV lead was implanted in two, and in nine patients, after reviewing the CS venogram, a new CS lead insertion was successfully attempted. CONCLUSION: Dual RV pacing is associated with worse clinical outcomes and higher complication rates than conventional CRT.

Tramadol for neuropathic pain in adults.

BACKGROUND: This review is an update of a review of tramadol for neuropathic pain, published in 2006; updating was to bring the review in line with current standards. Neuropathic pain, which is caused by a lesion or disease affecting the somatosensory system, may be central or peripheral in origin. Peripheral neuropathic pain often includes symptoms such as burning or shooting sensations, abnormal sensitivity to normally painless stimuli, or an increased sensitivity to normally painful stimuli. Neuropathic pain is a common symptom in many diseases of the peripheral nervous system. OBJECTIVES: To assess the analgesic efficacy of tramadol compared with placebo or other active interventions for chronic neuropathic pain in adults, and the adverse events associated with its use in clinical trials. SEARCH METHODS: We searched CENTRAL, MEDLINE, and Embase for randomised controlled trials from inception to January 2017. We also searched the reference lists of retrieved studies and reviews, and online clinical trial registries. SELECTION CRITERIA: We included randomised, double-blind trials of two weeks' duration or longer, comparing tramadol (any route of administration) with placebo or another active treatment for neuropathic pain, with subjective pain assessment by the participant. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed trial quality and potential bias. Primary outcomes were participants with substantial pain relief (at least 50% pain relief over baseline or very much improved on Patient Global Impression of Change scale (PGIC)), or moderate pain relief (at least 30% pain relief over baseline or much or very much improved on PGIC). Where pooled analysis was possible, we used dichotomous data to calculate risk ratio (RR) and number needed to treat for an additional beneficial outcome (NNT) or harmful outcome (NNH), using standard methods. We assessed the quality of the evidence using GRADE and created 'Summary of findings' tables. MAIN RESULTS: We identified six randomised, double-blind studies involving 438 participants with suitably characterised neuropathic pain. In each, tramadol was started at a dose of about 100 mg daily and increased over one to two weeks to a maximum of 400 mg daily or the maximum tolerated dose, and then maintained for the remainder of the study. Participants had experienced moderate or severe neuropathic pain for at least three months due to cancer, cancer treatment, postherpetic neuralgia, peripheral diabetic neuropathy, spinal cord injury, or polyneuropathy. The mean age was 50 to 67 years with approximately equal numbers of men and women. Exclusions were typically people with other significant comorbidity or pain from other causes. Study duration for treatments was four to six weeks, and two studies had a cross-over design.Not all studies reported all the outcomes of interest, and there were limited data for pain outcomes. At least 50% pain intensity reduction was reported in three studies (265 participants, 110 events). Using a random-effects analysis, 70/132 (53%) had at least 50% pain relief with tramadol, and 40/133 (30%) with placebo; the risk ratio (RR) was 2.2 (95% confidence interval (CI) 1.02 to 4.6). The NNT calculated from these data was 4.4 (95% CI 2.9 to 8.8). We downgraded the evidence for this outcome by two levels to low quality because of the small size of studies and of the pooled data set, because there were only 110 actual events, the analysis included different types of neuropathic pain, the studies all had at least one high risk of potential bias, and because of the limited duration of the studies.Participants experienced more adverse events with tramadol than placebo. Report of any adverse event was higher with tramadol (58%) than placebo (34%) (4 studies, 266 participants, 123 events; RR 1.6 (95% CI 1.2 to 2.1); NNH 4.2 (95% CI 2.8 to 8.3)). Adverse event withdrawal was higher with tramadol (16%) than placebo (3%) (6 studies, 485 participants, 45 events; RR 4.1 (95% CI 2.0 to 8.4); NNH 8.2 (95% CI 5.8 to 14)). Only four serious adverse events were reported, without obvious attribution to treatment, and no deaths were reported. We downgraded the evidence for this outcome by two or three levels to low or very low quality because of small study size, because there were few actual events, and because of the limited duration of the studies. AUTHORS' CONCLUSIONS: There is only modest information about the use of tramadol in neuropathic pain, coming from small, largely inadequate studies with potential risk of bias. That bias would normally increase the apparent benefits of tramadol. The evidence of benefit from tramadol was of low or very low quality, meaning that it does not provide a reliable indication of the likely effect, and the likelihood is very high that the effect will be substantially different from the estimate in this systematic review.

Adding Defibrillation Therapy to Cardiac Resynchronization on the Basis of the Myocardial Substrate.

BACKGROUND: Patients with nonischemic dilated cardiomyopathy (DCM) may be at lower risk for ventricular arrhythmias compared with those with ischemic cardiomyopathy (ICM). In addition, DCM has been identified as a predictor of positive response to cardiac resynchronization therapy (CRT). OBJECTIVES: The aim of this study was to investigate the impact of an additional implantable cardioverter-defibrillator over CRT, according to underlying heart disease, in a large study group of primary prevention patients with heart failure. METHODS: This was an observational, multicenter, European cohort study of 5,307 consecutive patients with DCM or ICM, no history of sustained ventricular arrhythmias, who underwent CRT implantation with (n = 4,037) or without (n = 1,270) a defibrillator. Propensity-score and cause-of-death analyses were used to compare outcomes. RESULTS: After a mean follow-up period of 41.4 ± 29.0 months, patients with ICM had better survival when receiving CRT with a defibrillator compared with those who received CRT without a defibrillator (hazard ratio for mortality adjusted on propensity score and all mortality predictors: 0.76; 95% confidence interval [CI]: 0.62 to 0.92; p = 0.005), whereas in patients with DCM, no such difference was observed (hazard ratio: 0.92; 95% CI: 0.73 to 1.16; p = 0.49). Compared with recipients of defibrillators, the excess mortality in patients who did not receive defibrillators was related to sudden cardiac death in 8.0% among those with ICM but in only 0.4% of those with DCM. CONCLUSIONS: Among patients with heart failure with indications for CRT, those with DCM may not benefit from additional primary prevention implantable cardioverter-defibrillator therapy, as opposed to those with ICM.

Sex-specific outcomes with addition of defibrillation to resynchronisation therapy in patients with heart failure.

OBJECTIVE: Among primary prevention patients with heart failure receiving cardiac resynchronisation therapy (CRT), the impact of additional implantable cardioverter defibrillator (ICD) treatment on outcomes and its interaction with sex remains uncertain. We aim to assess whether the addition of the ICD functionality to CRT devices offers a more pronounced survival benefit in men compared with women, as previous research has suggested. METHODS: Observational multicentre cohort study of 5307 consecutive patients with ischaemic or non-ischaemic dilated cardiomyopathy and no history of sustained ventricular arrhythmias having CRT implantation with (cardiac resynchronisation therapy defibrillator (CRT-D), n=4037) or without (cardiac resynchronisation therapy pacemaker (CRT-P), n=1270) defibrillator functionality. Using propensity score (PS) matching and weighting and cause-of-death data, we assessed and compared the outcome of patients with CRT-D versus CRT-P. This analysis was stratified according to sex. RESULTS: After a median follow-up of 34 months (interquartile range 22-60 months) no survival advantage, of CRT-D versus CRT-P was observed in both men and women after PS matching (HR=0.95, 95% CI 0.77 to 1.16, p=0.61, and HR=1.30, 95% CI 0.83 to 2.04, p=0.25, respectively). With inverse-probability weighting, a benefit of CRT-D was seen in male patients (HR 0.78, 95% CI 0.65 to 0.94, p=0.012) but not in women (HR 0.87, 95% CI 0.63 to 1.19, p=0.43). The excess unadjusted mortality of patients with CRT-P compared with CRT-D was related to sudden cardiac death in 7.4% of cases in men but only 2.2% in women. CONCLUSIONS: In primary prevention patients with CRT indication, the addition of a defibrillator might convey additional benefit only in well-selected male patients.

Sleeping with the fishes: electromagnetic interference causing an inappropriate implantable cardioverter defibrillator shock.

A 60-year-old man with a cardiac defibrillator implanted due to previous ventricular fibrillation arrest and ischaemic cardiomyopathy received a shock while cleaning his fish pond. At the time, his immersed arm was close to a submersed water pump, but the patient was asymptomatic. As a result of the shock he lost consciousness, but collapsed backwards, away from the pond. Interrogation of the device revealed a high-frequency artefact that was sensed by the device and triggered a shock. Device parameters were otherwise normal. Subsequently, the submersed water pump was found to be the source of an external alternating current leak and was identified as the likely cause of the inappropriate shock due to electromagnetic interference (EMI). Awareness of potential sources of EMI along with evaluation of data with a detailed clinical history is warranted in all cases.

The survival time of chocolates on hospital wards: covert observational study.

OBJECTIVE: To quantify the consumption of chocolates in a hospital ward environment. DESIGN: Multicentre, prospective, covert observational study. SETTING: Four wards at three hospitals (where the authors worked) within the United Kingdom. PARTICIPANTS: Boxes of Quality Street (Nestlé) and Roses (Cadbury) on the ward and anyone eating these chocolates. INTERVENTION: Observers covertly placed two 350 g boxes of Quality Street and Roses chocolates on each ward (eight boxes were used in the study containing a total of 258 individual chocolates). These boxes were kept under continuous covert surveillance, with the time recorded when each chocolate was eaten. MAIN OUTCOME MEASURE: Median survival time of a chocolate. RESULTS: 191 out of 258 (74%) chocolates were observed being eaten. The mean total observation period was 254 minutes (95% confidence interval 179 to 329). The median survival time of a chocolate was 51 minutes (39 to 63). The model of chocolate consumption was non-linear, with an initial rapid rate of consumption that slowed with time. An exponential decay model best fitted these findings (model R(2)=0.844, P<0.001), with a survival half life (time taken for 50% of the chocolates to be eaten) of 99 minutes. The mean time taken to open a box of chocolates from first appearance on the ward was 12 minutes (95% confidence interval 0 to 24). Quality Street chocolates survived longer than Roses chocolates (hazard ratio for survival of Roses v Quality Street 0.70, 95% confidence interval 0.53 to 0.93, P=0.014). The highest percentages of chocolates were consumed by healthcare assistants (28%) and nurses (28%), followed by doctors (15%). CONCLUSIONS: From our observational study, chocolate survival in a hospital ward was relatively short, and was modelled well by an exponential decay model. Roses chocolates were preferentially consumed to Quality Street chocolates in a ward setting. Chocolates were consumed primarily by healthcare assistants and nurses, followed by doctors. Further practical studies are needed.

Delayed conduction and its implications in murine Scn5a(+/-) hearts: independent and interacting effects of genotype, age, and sex.

We explored for relationships between SCN5A haploinsufficiency, implicated in clinical arrhythmogenicity, and right ventricular (RV) conduction disorders in Langendorff-perfused, male and female, and young (3 months) and old (>12 month old) Scn5a ( +/-) and wild type (WT) hearts. The investigated conditions of genotype, age, and sex affected latencies but not repolarization time courses of RV monophasic action potentials. This prompted examination of the patterns of RV epicardial activation, its dispersion, and their interrelationships as possible arrhythmic mechanisms using a 64-channel, multi-electrode array. Mean ventricular activation times (T*(MEAN)), spatial dispersions (D* (S)) between recording channels/cardiac cycle, and maximum activation times (T* (MAX)) representing the slowest possible conduction in any given heart were all higher in old male Scn5a ( +/-) compared with young male and old female Scn5a ( +/-) and old male WT. Temporal dispersions (D*(T)) of recording channels were similarly higher in old male Scn5a (+/-) compared with old male WT. All groupings of D*(T), D*(S), and T*(MAX) nevertheless linearly correlated with T*(MEAN), with indistinguishable slopes. The variates explored thus influence D*(T), D*(S), and T*(MAX) through actions on T*(MEAN). These findings in turn correlated with increased levels of fibrosis in young male, young female, and old male Scn5a ( +/-) compared with the corresponding WTs. We thus demonstrate for the first time independent and interacting effects of genotype, age, and sex on epicardial conduction and its dispersions at least partially attributable to fibrotic change, resulting in the greatest effects in old male Scn5a ( +/-) in an absence of alterations in repolarization time courses. This directly implicates altered depolarization in the clinical arrhythmogenicity associated with Scn5a ( +/-).

Atrial arrhythmogenicity in aged Scn5a+/DeltaKPQ mice modeling long QT type 3 syndrome and its relationship to Na+ channel expression and cardiac conduction.

Recent studies have reported that human mutations in Nav1.5 predispose to early age onset atrial arrhythmia. The present experiments accordingly assess atrial arrhythmogenicity in aging Scn5a+/KPQ mice modeling long QT3 syndrome in relationship to cardiac Na(+) channel, Nav1.5, expression. Atrial electrophysiological properties in isolated Langendorff-perfused hearts from 3- and 12-month-old wild type (WT), and Scn5a+/KPQ mice were assessed using programmed electrical stimulation and their Nav1.5 expression assessed by Western blot. Cardiac conduction properties were assessed electrocardiographically in intact anesthetized animals. Monophasic action potential recordings demonstrated increased atrial arrhythmogenicity specifically in aged Scn5a+/DeltaKPQ hearts. These showed greater action potential duration/refractory period ratios but lower atrial Nav1.5 expression levels than aged WT mice. Atrial Nav1.5 levels were higher in young Scn5a+/DeltaKPQ than young WT. These levels increased with age in WT but not Scn5a+/DeltaKPQ. Both young and aged Scn5a+/DeltaKPQ mice showed lower heart rates and longer PR intervals than their WT counterparts. Young Scn5a+/DeltaKPQ mice showed longer QT and QTc intervals than young WT. Aged Scn5a+/DeltaKPQ showed longer QRS durations than aged WT. PR intervals were prolonged and QT intervals were shortened in young relative to aged WT. In contrast, ECG parameters were similar between young and aged Scn5a+/DeltaKPQ. Aged murine Scn5a+/DeltaKPQ hearts thus exhibit an increased atrial arrhythmogenicity. The differing Nav1.5 expression and electrocardiographic indicators of slowed cardiac conduction between Scn5a+/DeltaKPQ and WT, which show further variations associated with aging, may contribute toward atrial arrhythmia in aged Scn5a+/DeltaKPQ hearts.

Cardiac Remote Ischemic Preconditioning in Coronary Stenting (CRISP Stent) Study: a prospective, randomized control trial.

BACKGROUND: Myocyte necrosis as a result of elective percutaneous coronary intervention (PCI) occurs in approximately one third of cases and is associated with subsequent cardiovascular events. This study assessed the ability of remote ischemic preconditioning (IPC) to attenuate cardiac troponin I (cTnI) release after elective PCI. METHODS AND RESULTS: Two hundred forty-two consecutive patients undergoing elective PCI with undetectable preprocedural cTnI were recruited. Subjects were randomized to receive remote IPC (induced by three 5-minute inflations of a blood pressure cuff to 200 mm Hg around the upper arm, followed by 5-minute intervals of reperfusion) or control (an uninflated cuff around the arm) before arrival in the catheter laboratory. The primary outcome was cTnI at 24 hours after PCI. Secondary outcomes included renal dysfunction and major adverse cardiac and cerebral event rate at 6 months. The median cTnI at 24 hours after PCI was lower in the remote IPC compared with the control group (0.06 versus 0.16 ng/mL; P=0.040). After remote IPC, cTnI was <0.04 ng/mL in 44 patients (42%) compared with 24 in the control group (24%; P=0.01). Subjects who received remote IPC experienced less chest discomfort (P=0.0006) and ECG ST-segment deviation (P=0.005) than control subjects. At 6 months, the major adverse cardiac and cerebral event rate was lower in the remote IPC group (4 versus 13 events; P=0.018). CONCLUSIONS: Remote IPC reduces ischemic chest discomfort during PCI, attenuates procedure-related cTnI release, and appears to reduce subsequent cardiovascular events.