Renal function and the long-term clinical outcomes of cardiac resynchronization therapy with or without defibrillation.

BACKGROUND AND AIMS: Patients with moderate-to-severe chronic kidney disease (CKD) are underrepresented in clinical trials of cardiac resynchronization therapy (CRT)-defibrillation (CRT-D) or CRT-pacing (CRT-P). We sought to determine whether outcomes after CRT-D are better than after CRT-P over a wide spectrum of CKD. METHODS AND RESULTS: Clinical events were quantified in relation to preimplant estimated glomerular filtration rate (eGFR) after CRT-D (n = 410 [39.2%]) or CRT-P (n = 636 [60.8%]) implantation. Over a follow-up period of 3.7 years (median, interquartile range: 2.1-5.7), the eGFR < 60 group (n = 598) had a higher risk of total mortality (adjusted hazard ratio [aHR]: 1.28; P = 0.017), total mortality or heart failure (HF) hospitalization (aHR: 1.32; P = 0.004), total mortality or hospitalization for major adverse cardiac events (MACEs, aHR: 1.34; P = 0.002), and cardiac mortality (aHR: 1.33; P = 0.036), compared to the eGFR ≥ 60 group (n = 448), after covariate adjustment. In analyses of CRT-D versus CRT-P, CRT-D was associated with a lower risk of total mortality (eGFR ≥ 60 HR: 0.65; P = 0.028; eGFR < 60 HR: 0.64, P = 0.002), total mortality or HF hospitalization (eGFR ≥ 60 aHR: 0.66; P = 0.021; eGFR < 60 aHR: 0.69, P = 0.007), total mortality or hospitalization for MACEs (eGFR ≥ 60 aHR: 0.70; P = 0.039; eGFR < 60 aHR: 0.69, P = 0.005), and cardiac mortality (eGFR ≥ 60 aHR: 0.60; P = 0.026; eGFR < 60 aHR: 0.55; P = 0.003). CONCLUSION: In CRT recipients, moderate CKD is associated with a higher mortality and morbidity compared to normal renal function or mild CKD. Despite less favorable absolute outcomes, patients with moderate CKD had better outcomes after CRT-D than after CRT-P.

Long-Term Outcomes of Cardiac Resynchronization Therapy Using Apical Versus Nonapical Left Ventricular Pacing.

Background Experimental evidence indicates that left ventricular ( LV ) apical pacing is hemodynamically superior to nonapical LV pacing. Some studies have shown that an LV apical lead position is unfavorable in cardiac resynchronization therapy. We sought to determine whether an apical LV lead position influences cardiac mortality after cardiac resynchronization therapy. Methods and Results In this retrospective observational study, the primary end point of cardiac mortality was assessed in relation to longitudinal (basal, midventricular, or apical) and circumferential (anterior, lateral, or posterior) LV lead positions, as well as right ventricular (apical or septal), assigned using fluoroscopy. Lead positions were assessed in 1189 patients undergoing cardiac resynchronization therapy implantation over 15 years. After a median follow-up of 6.0 years (interquartile range: 4.4-7.7 years), an apical LV lead position was associated with lower cardiac mortality than a nonapical position (adjusted hazard ratio: 0.74; 95% confidence interval, 0.56-0.99) after covariate adjustment. There were no differences in total mortality or heart failure hospitalization. Death from pump failure was lower with apical than nonapical positions (adjusted hazard ratio: 0.69; 95% confidence interval, 0.51-0.94). Compared with a basal position, an apical LV position was also associated with lower risk of sudden cardiac death (adjusted hazard ratio: 0.34; 95% confidence interval, 0.13-0.93). No differences emerged between circumferential LV lead positions or right ventricular positions with respect to any end point. Conclusions In recipients of cardiac resynchronization therapy, an apical LV lead position was associated with better long-term cardiac survival than a nonapical position. This effect was due to a lower risk of pump failure and sudden cardiac death.

Long-term clinical outcomes of cardiac resynchronization therapy with or without defibrillation: impact of the aetiology of cardiomyopathy.

Aims: There is a continuing debate as to whether cardiac resynchronization therapy-defibrillation (CRT-D) is superior to CRT-pacing (CRT-P), particularly in patients with non-ischaemic cardiomyopathy (NICM). We sought to quantify the clinical outcomes after primary prevention of CRT-D and CRT-P and identify whether these differed according to the aetiology of cardiomyopathy. Methods and results: Analyses were undertaken in the total study population of patients treated with CRT-D (n = 551) or CRT-P (n = 999) and in propensity-matched samples. Device choice was governed by the clinical guidelines in the United Kingdom. In univariable analyses of the total study population, for a maximum follow-up of 16 years (median 4.7 years, interquartile range 2.4-7.1), CRT-D was associated with a lower total mortality [hazard ratio (HR) 0.72] and the composite endpoints of total mortality or heart failure (HF) hospitalization (HR 0.72) and total mortality or hospitalization for major adverse cardiac events (MACE; HR 0.71) (all P < 0.001). After propensity matching (n = 796), CRT-D was associated with a lower total mortality (HR 0.72) and the composite endpoints (all P < 0.01). When further stratified according to aetiology, CRT-D was associated with a lower total mortality (HR 0.62), total mortality or HF hospitalization (HR 0.63), and total mortality or hospitalization for MACE (HR 0.59) (all P < 0.001) in patients with ischaemic cardiomyopathy (ICM). There were no differences in outcomes between CRT-D and CRT-P in patients with NICM. Conclusion: In this study of real-world clinical practice, CRT-D was superior to CRT-P with respect to total mortality and composite endpoints, independent of known confounders. The benefit of CRT-D was evident in ICM but not in NICM.

Clinical outcomes after upgrading from pacemakers to cardiac resynchronization therapy.

BACKGROUND AND AIMS: Right ventricular pacing may lead to heart failure (HF). Upgrades from pacemakers to cardiac resynchronization therapy (CRT) were excluded from most randomized, controlled trials. We sought to determine the long-term outcomes of upgrading from pacemakers to CRT with (CRT-D) or without (CRT-P) defibrillation in patients with no history of sustained ventricular arrhythmias. METHODS AND RESULTS: In this observational study, clinical events were quantified in relation to the type of implant (de novo or upgrade) and device type at upgrade (CRT-P or CRT-D). Patients underwent CRT implantation (n = 1,545; 1,314 [85%] de novo implants and 231 [15%] upgrades) over a median of 4.6 years [interquartile range: 2.4-7.0]. In analyses of crude event rates, upgrades had a higher total mortality (adjusted hazard ratio [aHR]: 1.33; 95% confidence interval [CI] 0.10-1.61), a higher total mortality or HF hospitalization (aHR: 1.26; 95% CI 1.05-1.51), but similar mortality or hospitalization for major adverse cardiac events (MACEs, aHR: 1.15; 95% CI 0.96-1.38). No group differences emerged in any of these endpoints after propensity score matching. After inverse probability weighting in upgrades, total mortality (HR: 0.55; 95% CI 0.36-0.73), total mortality or HF hospitalization (HR: 0.56; 95% CI 0.34-0.79), and total mortality or hospitalization for MACEs (HR: 0.61; 95% CI 0.40-0.82) were lower after CRT-D than after CRT-P. CONCLUSION: Upgrading from pacemakers to CRT was associated with a similar long-term risk of mortality and morbidity to de novo CRT. After upgrade, CRT-D was associated with a lower mortality than CRT-P.

Outcomes of Cardiac Resynchronization Therapy With or Without Defibrillation in Patients With Nonischemic Cardiomyopathy.

BACKGROUND: Recent studies have cast doubt on the benefit of cardiac resynchronization therapy (CRT) with defibrillation (CRT-D) versus pacing (CRT-P) for patients with nonischemic cardiomyopathy (NICM). Left ventricular myocardial scar portends poor clinical outcomes. OBJECTIVES: The aim of this study was to determine whether CRT-D is superior to CRT-P in patients with NICM either with (+) or without (-) left ventricular midwall fibrosis (MWF), detected by cardiac magnetic resonance. METHODS: Clinical events were quantified in patients with NICM who were +MWF (n = 68) or -MWF (n = 184) who underwent cardiac magnetic resonance prior to CRT device implantation. RESULTS: In the total study population, +MWF emerged as an independent predictor of total mortality (adjusted hazard ratio [aHR]: 2.31; 95% confidence interval [CI]: 1.45 to 3.68), total mortality or heart failure hospitalization (aHR: 2.02; 95% CI: 1.32 to 3.09), total mortality or hospitalization for major adverse cardiac events (aHR: 2.02; 95% CI: 1.32 to 3.07), death from pump failure (aHR: 1.95; 95% CI: 1.11 to 3.41), and sudden cardiac death (aHR: 3.75; 95% CI: 1.26 to 11.2) over a maximum follow-up period of 14 years (median 3.8 years [interquartile range: 2.0 to 6.1 years] for +MWF and 4.6 years [interquartile range: 2.4 to 8.3 years] for -MWF). In separate analyses of +MWF and -MWF, total mortality (aHR: 0.23; 95% CI: 0.07 to 0.75), total mortality or heart failure hospitalization (aHR: 0.32; 95% CI: 0.12 to 0.82), and total mortality or hospitalization for major adverse cardiac events (aHR: 0.30; 95% CI: 0.12 to 0.78) were lower after CRT-D than after CRT-P in +MWF but not in -MWF. CONCLUSIONS: In patients with NICM, CRT-D was superior to CRT-P in +MWF but not -MWF. These findings have implications for the choice of device therapy in patients with NICM.

Making models to simulate testicular swellings.

BACKGROUND: Testicular examination and the recognition of common scrotal swellings is a key clinical skill that is difficult to teach undergraduates because of its intimate nature. A novel approach for this topic was prompted by the description of handmade models in the medical literature to teach anatomical knowledge and clinical skills. METHODS: Affordable low-cost materials were purchased and assembled to form six models replicating key scrotal pathologies: epididymal cyst, epididymitis, hydrocoele, inguinoscrotal hernia, testicular tumour and varicocoele. They were used to teach the examination of testicular swellings to undergraduate medical students alongside a rubber manikin exhibiting testicular tumours, and all participants were invited to complete a post-session evaluation on their experiences. RESULTS: There were 66 participants in total: 83.3 per cent felt that the handmade models were more beneficial and 81.8 per cent would recommend them to colleagues to train in testicular examination, rather than the rubber model. The most common reasons provided were the greater variety of pathologies demonstrated, separate models for each pathology and the presence of key diagnostic features for certain swellings. The recognition of common scrotal swellings is a key clinical skill that is difficult to teach undergraduates DISCUSSION: These models took approximately 1 hour to assemble. We hope that they can be widely used by Urology departments as a cost-effective aid in the practical teaching of testicular examination and recognition of common scrotal swellings, thus reducing the dependency and intimacy of examining real patients with clinical signs.

Long-Term Follow-Up of Isolated Epicardial Left Ventricular Lead Implant Using a Minithoracotomy Approach for Cardiac Resynchronization Therapy.

BACKGROUND: Transvenous left ventricular (LV) lead placement for cardiac resynchronization therapy is unsuccessful in 5-10% of reported cases. These patients may benefit from isolated surgical placement of an epicardial LV lead via minithoracotomy approach. AIM: To evaluate the success of this approach at long-term follow-up. METHODS: Retrospective evaluation of all consecutive patients undergoing isolated epicardial LV lead placement after failed transvenous attempt over a 6-year period. Data collected on baseline parameters, procedural details, and outcome at follow-up (hospital stay, complications, mortality, and clinical response). RESULTS: Forty-two patients underwent epicardial lead implant. Five died within 1 year (11.9%): two (4.8%) died within 30-days post op (one from intraoperative hemorrhage, the other from multiple organ failure); 39 (95.1%) were admitted to the high dependency unit and transferred to the ward <24 hours. Median hospital stay was 3.4 ± 1.9 days. The overall complication rate was 17.5% (n = 7): 15.0% (n = 6) short term and 2.5% (n = 1) long term; these included three (7.5%) LV noncapture events all treated with reprogramming. There were two (5.0%) wound infections requiring oral antibiotics and two (5.0%) device infections requiring intravenous antibiotics (one had device resiting, the other developed septic shock requiring intensive care admission). Assessment of clinical response was possible in 34 (81.0%) at follow-up: 21 (61.8%) were responders and 13 (28.2%) nonresponders with no significant differences between these groups; no clinical predictors of response were identified. CONCLUSION: Isolated epicardial LV lead implant using minithoracotomy is relatively safe and effective at successful LV pacing. Response rate and postoperative recovery at long-term follow-up are reasonable in these high-risk patients.

Left ventricular lead position, mechanical activation, and myocardial scar in relation to left ventricular reverse remodeling and clinical outcomes after cardiac resynchronization therapy: A feature-tracking and contrast-enhanced cardiovascular magnetic resonance study.

BACKGROUND: Late mechanical activation (LMA) and viability in the left ventricular (LV) myocardium have been proposed as targets for LV pacing during cardiac resynchronization therapy (CRT). OBJECTIVE: The purpose of this study was to determine whether an LV lead position over segments with LMA and no scar improves LV reverse remodeling (LVRR) and clinical outcomes after CRT. METHODS: Feature-tracking and late gadolinium enhancement images were analyzed retrospectively in patients with heart failure (HF) (n = 89; mean age 66.8 ± 10.8 years; LV ejection fraction = 23.1% ± 9.9%) who underwent cardiovascular magnetic resonance (CMR) scanning before CRT implantation. Lead positions were classified as concordant (no scar and LMA [time to peak systolic circumferential strain]) or nonconcordant (scar and/or no LMA). RESULTS: LVRR occurred in 68% and 24% of patients with concordant and nonconcordant LV lead positions, respectively (P < .001). Over a median of 4.4 years (range 0.1-8.7 years), LV lead concordance predicted cardiac mortality (adjusted odds ratio [aOR] 0.27; 95% confidence interval [CI] 0.12-0.62) and cardiac mortality or HF hospitalizations (aOR 0.26, 95% CI 0.12-0.58). "No scar" in the paced segment predicted cardiac mortality (aOR 0.24; 95% CI 0.11-0.52) and cardiac mortality or HF hospitalizations (adjusted aOR 0.24; 95% CI 0.12-0.49). CONCLUSION: LV lead deployment over nonscarred LMA segments was associated with better LVRR and clinical outcomes after CRT. LVRR was primarily related to LMA, whereas events were primarily related to scar. These findings support the use of late gadolinium enhancement CMR and feature-tracking CMR in guiding LV lead deployment.

Inflammatory myofibroblastic tumour at the pacemaker site.

Inflammatory myofibroblastic tumour (IMT) or inflammatory pseudotumour is a histologically distinctive lesion occurring primarily in the viscera and soft tissue of children and young adults. We report an unusual case of IMT which had undergone malignant transformation in the chest wall at the pacemaker site. A 64-year-old male presented with a history of high fever, loss of appetite and weight loss of three months duration. He had a dual chamber pacemaker reinserted in the left infraclavicular region in the previous year. This was followed by a gradually enlarging hard swelling at the insertion site. The CT-scan showed a soft tissue mass encasing the pacing box, without intrathoracic extension. The trucut biopsy was suspicious of soft tissue sarcoma. A well encapsulated hard mass, with pacemaker embedded within it was resected en-bloc ensuring wide resection margins. Histology revealed fascicles of spindle cell proliferation with prominent inflammatory component, occasional spindle cells with prominent nucleoli and scattered atypical mitotic figures, with areas of focal necrosis. The lesional cells were negative for CD21, smooth muscle actin, ckit, cytokeratins and anaplastic lymphoma kinase 1. A diagnosis of IMT with malignant transformation i.e. inflammatory fibrosarcoma was made. He had adjuvant radiotherapy and uneventful recovery.

Abnormal subendocardial perfusion in cardiac syndrome X detected by cardiovascular magnetic resonance imaging.

BACKGROUND: In cardiac syndrome X (a syndrome characterized by typical angina, abnormal exercise-test results, and normal coronary arteries), conventional investigations have not found that chest pain is due to myocardial ischemia. Magnetic resonance techniques have higher resolution and therefore may be more sensitive. METHODS: We performed myocardial-perfusion cardiovascular magnetic resonance imaging in 20 patients with syndrome X and 10 matched controls, both at rest and during an infusion of adenosine. Quantitative perfusion analysis was performed by using the normalized upslope of myocardial signal enhancement to derive the myocardial perfusion index and the myocardial-perfusion reserve index (defined as the ratio of the myocardial perfusion index during stress to the index at rest). RESULTS: In the controls, the myocardial perfusion index increased in both myocardial layers with adenosine (in the subendocardium, from a mean [+/-SD] of 0.12+/-0.03 to 0.16+/-0.03 [P=0.02]; in the subepicardium, from 0.11+/-0.02 to 0.17+/-0.05 [P=0.002]); in patients with syndrome X, the myocardial perfusion index did not change significantly in the subendocardium (0.13+/-0.02 vs. 0.14+/-0.03, P=0.11; P=0.09 as compared with controls) but increased in the subepicardium (from 0.11+/-0.02 to 0.20+/-0.04, P<0.001; P=0.11 for the comparison with controls). Adenosine provoked chest pain in 95 percent of patients with syndrome X and 40 percent of controls (P<0.001). CONCLUSIONS: In patients with syndrome X, cardiovascular magnetic resonance imaging demonstrates subendocardial hypoperfusion during the intravenous administration of adenosine, which is associated with intense chest pain. These data support the notion that the chest pain may have an ischemic cause.