Faculty Bibliography

BACKGROUND:Atrial fibrillation (AF), the most common sustained arrhythmia in hypertrophic cardiomyopathy (HCM), is capable of producing symptoms that impact quality of life and is associated with risk for embolic stroke. However, the influence of AF on clinical course and outcome in HCM remains incompletely resolved. METHODS:Records of 1558 consecutive patients followed at the Tufts Medical Center Hypertrophic Cardiomyopathy Institute for 4.8±3.4 years (from 2004 to 2014) were accessed. RESULTS:<0.001). CONCLUSIONS:Transient symptomatic episodes of AF, often responsible for impaired quality of life, are unpredictable in frequency and timing, but amenable to effective contemporary treatments, and infrequently progress to permanent AF. AF is not a major contributor to heart failure morbidity or a cause of arrhythmic sudden death; when treated, it is associated with low disease-related mortality, no different than for patients without AF. AF is an uncommon primary cause of death in HCM virtually limited to embolic stroke, supporting a low threshold for initiating anticoagulation therapy.

Hypertrophic cardiomyopathy (HC) has been characterized as a generally progressive genetic heart disease, creating an ominous perspective for patients and managing cardiologists. We explored the HC disease burden and interaction of adverse clinical pathways to clarify patient expectations over long time periods in the contemporary therapeutic era. We studied 1,000 consecutive HC patients (52 ± 17 years) at Tufts Medical Center, followed 9.3 ± 8 years from diagnosis, employing a novel disease pathway model: 46% experienced a benign course free of adverse pathways, but 42% of patients progressed along 1 major pathway, most commonly refractory heart failure to New York Heart Association class III or IV requiring surgical myectomy (or alcohol ablation) or heart transplant; repetitive or permanent atrial fibrillation; and least commonly arrhythmic sudden death events. Eleven percent experienced 2 of these therapeutic end points at different times in their clinical course, most frequently the combination of advanced heart failure and atrial fibrillation, whereas only 1% incurred all 3 pathways. Freedom of progression from 1 to 2 disease pathways, or from 2 to 3 was 80% and 93% at 5 years, respectively. Annual HC-related mortality did not differ according to the number of pathways: 1 (0.8%), 2 (0.8%), or 3 (2.4%) (p = 0.56), and 93% of patients were in New York Heart Association classes I or II at follow-up. In conclusion, it is uncommon for HC patients to experience multiple adverse (but treatable) disease pathways, underscoring the principle that HC is not a uniformly progressive disease. These observations provide a measure of clarity and/or reassurance to patients regarding the true long-term disease burden of HC.

BACKGROUND:Arterial stiffness, a composite indicator of vascular health and predictor of future cardiovascular (CV) disease and events, was assessed in low-risk, uncomplicated pregnancies. METHODS:Women with low-risk pregnancy were recruited consecutively (recruitment across the 3 trimesters). Vessel hemodynamics and arterial stiffness were measured every 4 weeks from recruitment until delivery and at 6.5 weeks postpartum. RESULTS:Sixty-three women (maternal age: 32.7 ± 4.9 years) with low-risk, uncomplicated pregnancy were recruited. Mean arterial pressure (P = .04) and aortic pulse pressure (P = .03) decreased during pregnancy, whereas heart rate gradually increased until delivery (P = .0002) and decreased postpartum (P = .06). Pulse pressure amplification (PPA) and carotid-to-radial pulse wave velocity initially decreased in the second trimester, followed by a steady increase until delivery (P = .01 and P = .04, respectively). Interestingly, PPA sharply decreased postpartum (P = .01). Augmentation index and the subendocardial viability ratio significantly increased postpartum (P = .03 and .02, respectively). CONCLUSION/CONCLUSIONS:The PPA increased steadily after the second trimester and was sharply decreased postpartum in low-risk, uncomplicated pregnancy. Longer and larger longitudinal studies will evaluate changes in PPA and its potential as a marker of CV risk later in women's life.

Background. Transarterial chemoembolization (TACE) has been investigated in patients with liver metastases from colorectal cancer (LMCRC). Limited experience and available data suggest that TACE can achieve disease stabilization or improvement, even in heavily pretreated patients. Methods. Patients with LMCRC, ECOG 0-2, who failed at least 1 line of systemic chemotherapy, received embolizations with 2 mL of microspheres preloaded with 100 mg of irinotecan. Beads were delivered selectively into hepatic arteries. Primary endpoint was overall survival (OS), analyzed using the Kaplan-Meier method. Secondary endpoint was safety, assessed using CTCAE version 4.0. Results. 27 patients were treated using DEBIRI. Patient median age was 57 years (range was 45-82 years). The median number of total embolizations was 1.3 (range 1-3). The median OS was 5.4 months (95% CI; 1.1-22.7 months). The most reported postembolization events were nausea (8/27), vomiting (6/27), right upper quadrant pain (16/27), fatigue (9/27), and the development of ascites (6/27). 5/26 patients required hospitalization after TACE for severe pain. Hospitalization was also required for 1 case of allergic reaction and 1 case of infection. Conclusion. Our data suggest that TACE with DEBIRI could be efficacious in a palliative setting for patients with LMCRC, but they do not necessarily support routine use in clinical practice.

A systematic review and meta-analysis was conducted using MEDLINE, EMBASE, and the Cochrane Library to investigate the association between preeclampsia and arterial stiffness. Twenty-three relevant studies were included. A significant increase in all arterial stiffness indices combined was observed in women with preeclampsia vs. women with normotensive pregnancies [standardized mean difference 1.62, 95% confidence interval (CI) 0.73-2.50]; carotid-femoral pulse wave velocity (cfPWV) and augmentation index (AIx) were also significantly increased (weighted mean difference, WMDcfPWV 1.04, 95% CI 0.34-1.74; WMDAIx 15.10, 95% CI 5.08-25.11), whereas carotid-radial PWV (crPWV) increase did not reach significance (WMDcrPWV 0.99, 95% CI -0.07 to 2.05). Significant increases in arterial stiffness measurements were noted in women with preeclampsia compared with those with gestational hypertension. Arterial stiffness measurements may also be useful in predicting preeclampsia and may play a role in the increased risk of future cardiovascular complications seen in women with a history of preeclampsia.

A systematic literature review was conducted using PubMed, Embase and the Cochrane Library to determine the effect of acute, chronic and passive smoking on arterial stiffness and to determine whether these effects are reversible after smoking cessation. A total of 39 relevant studies were identified and included. Acute smoking was found to cause an acute increase in arterial stiffness. Similarly, passive smoking increased arterial stiffness acutely and chronically. The majority of studies identified chronic smoking as a risk factor for increasing arterial stiffness. However, some studies found no statistical difference in arterial stiffness between nonsmokers and long-term smokers, although chronic smoking seems to sensitize the arterial response to acute smoking. In addition, whether arterial stiffness is reversed after smoking cessation and the timeline in which this may occur could not be determined from the identified literature. The effect of smoking discontinuation on arterial stiffness remains to be established by prospective smoking cessation trials.