Ryan S. Cantor

First Annual IMACS Report: A global International Society for Heart and Lung Transplantation Registry for Mechanical Circulatory Support.

The first annual report of the International Society for Heart and Lung Transplantation (ISHLT) Mechanically Assisted Circulatory Support (IMACS) registry provides global data on 5,942 patients from 31 countries. This initial report focuses on patient demographics, survival, device types, adverse events, competing outcomes, and a risk factor analysis.

Adverse events in children implanted with ventricular assist devices in the United States: Data from the Pediatric Interagency Registry for Mechanical Circulatory Support (PediMACS)

BACKGROUND Ventricular assist devices (VADs) have been used in children on an increasing basis in recent years. One-year survival rates are now >80% in multiple reports. In this report we describe adverse events experienced by children with durable ventricular assist devices, using a national-level registry (PediMACS, a component of INTERMACS) METHODS: PediMACS is a national registry that contains clinical data on patients who are <19 years of age at the time of VAD implantation. Data collection concludes at the time of VAD explantation. All FDA-approved devices are included. PediMACS was launched on September 1, 2012, and this report includes all data from launch until August 2014. Adverse events were coded with a uniform, pre-specified set of definitions. RESULTS This report comprises data from 200 patients with a median age of 11 years (range 11 days to 18 years), and total follow-up of 783 patient-months. The diagnoses were cardiomyopathy (n = 146, 73%), myocarditis (n = 17, 9%), congenital heart disease (n = 35, 18%) and other (n = 2, 1%). Pulsatile-flow devices were used in 91 patients (45%) and continuous-flow devices in 109 patients (55%). Actuarial survival was 81% at 6 months. There were 418 adverse events reported. The most frequent events were device malfunction (n = 79), infection (n = 78), neurologic dysfunction (n = 52) and bleeding (n = 68). Together, these accounted for 277 events, 66% of the total. Although 38% of patients had no reported adverse event and 16% of patients had ≥5 adverse events. Adverse events occurred at all time-points after implantation, but were most likely to occur in the first 30 days. For continuous-flow devices, there were broad similarities in adverse event rates between this cohort and historic rates from the INTERMACS population. CONCLUSIONS In this study cohort, the overall rate of early adverse events (within 90 days of implantation) was 86.3 events per 100 patient-months, and of late adverse events it was 20.4 events per 100 patient-months. The most common adverse events in recipients of pulsatile VADs were device malfunction, neurologic dysfunction, bleeding and infection. For continuous-flow VADs, the most common adverse events were infection, bleeding, cardiac arrhythmia, neurologic dysfunction and respiratory failure. Compared with an adult INTERMACS cohort, the overall rate and distribution of adverse events appears similar.

Outcomes of Patients With Peripartum Cardiomyopathy Who Received Mechanical Circulatory Support

Background— We describe the characteristics and outcomes of peripartum cardiomyopathy (PPCMP) patients who received durable mechanical circulatory support and compared it with other etiologies of advanced heart failure. Methods and Results— We analyzed 1258 women who were registered in Interagency Registry for Mechanically Assisted Circulatory Support between June 2006 and March 2012. Baseline characteristics, implant strategies, hemodynamics, echocardiographic data, and outcomes were compared. Ninety-nine women had PPCMP and 1159 had non-PPCMP as primary diagnosis. PPCMP women were younger ( P <0.001), more likely to be blacks, and had less comorbidities than non-PPCMP patients. PPCMP women had better survival than non-PPCMP women ( P =0.01) with a 2-year survival of 83%. Multivariable risk factor adjustment analysis showed that the improved survival was likely because of younger age and fewer comorbidities. At 36 months, a proportion of 48% PPCMP received heart transplantation. Recovery occurred at a frequency of 6% and 2% in the PPCMP and non-PPCMP groups ( P =0.1). Adverse event rates were similar in PPCMP and non-PPCMP patients except for higher cardiac arrhythmias and respiratory failure in the non-PPCMP in the first 3 months post implant. Conclusions— PPCMP women who receive durable mechanical circulatory support have a better survival than women with non-PPCPM. The improved survival observed in PPCMP is likely related to their fewer comorbidities and younger age. Myocardial recovery was uncommon and less than half of women with end-stage PPCPM received heart transplantation after 3 years of mechanical support.Background— We describe the characteristics and outcomes of peripartum cardiomyopathy (PPCMP) patients who received durable mechanical circulatory support and compared it with other etiologies of advanced heart failure. Methods and Results— We analyzed 1258 women who were registered in Interagency Registry for Mechanically Assisted Circulatory Support between June 2006 and March 2012. Baseline characteristics, implant strategies, hemodynamics, echocardiographic data, and outcomes were compared. Ninety-nine women had PPCMP and 1159 had non-PPCMP as primary diagnosis. PPCMP women were younger (P<0.001), more likely to be blacks, and had less comorbidities than non-PPCMP patients. PPCMP women had better survival than non-PPCMP women (P=0.01) with a 2-year survival of 83%. Multivariable risk factor adjustment analysis showed that the improved survival was likely because of younger age and fewer comorbidities. At 36 months, a proportion of 48% PPCMP received heart transplantation. Recovery occurred at a frequency of 6% and 2% in the PPCMP and non-PPCMP groups (P=0.1). Adverse event rates were similar in PPCMP and non-PPCMP patients except for higher cardiac arrhythmias and respiratory failure in the non-PPCMP in the first 3 months post implant. Conclusions— PPCMP women who receive durable mechanical circulatory support have a better survival than women with non-PPCPM. The improved survival observed in PPCMP is likely related to their fewer comorbidities and younger age. Myocardial recovery was uncommon and less than half of women with end-stage PPCPM received heart transplantation after 3 years of mechanical support.

Outcomes of Patients With Peripartum Cardiomyopathy Who Received Mechanical Circulatory Support Data From the Interagency Registry for Mechanically Assisted Circulatory Support

Background— We describe the characteristics and outcomes of peripartum cardiomyopathy (PPCMP) patients who received durable mechanical circulatory support and compared it with other etiologies of advanced heart failure. Methods and Results— We analyzed 1258 women who were registered in Interagency Registry for Mechanically Assisted Circulatory Support between June 2006 and March 2012. Baseline characteristics, implant strategies, hemodynamics, echocardiographic data, and outcomes were compared. Ninety-nine women had PPCMP and 1159 had non-PPCMP as primary diagnosis. PPCMP women were younger ( P <0.001), more likely to be blacks, and had less comorbidities than non-PPCMP patients. PPCMP women had better survival than non-PPCMP women ( P =0.01) with a 2-year survival of 83%. Multivariable risk factor adjustment analysis showed that the improved survival was likely because of younger age and fewer comorbidities. At 36 months, a proportion of 48% PPCMP received heart transplantation. Recovery occurred at a frequency of 6% and 2% in the PPCMP and non-PPCMP groups ( P =0.1). Adverse event rates were similar in PPCMP and non-PPCMP patients except for higher cardiac arrhythmias and respiratory failure in the non-PPCMP in the first 3 months post implant. Conclusions— PPCMP women who receive durable mechanical circulatory support have a better survival than women with non-PPCPM. The improved survival observed in PPCMP is likely related to their fewer comorbidities and younger age. Myocardial recovery was uncommon and less than half of women with end-stage PPCPM received heart transplantation after 3 years of mechanical support.Background— We describe the characteristics and outcomes of peripartum cardiomyopathy (PPCMP) patients who received durable mechanical circulatory support and compared it with other etiologies of advanced heart failure. Methods and Results— We analyzed 1258 women who were registered in Interagency Registry for Mechanically Assisted Circulatory Support between June 2006 and March 2012. Baseline characteristics, implant strategies, hemodynamics, echocardiographic data, and outcomes were compared. Ninety-nine women had PPCMP and 1159 had non-PPCMP as primary diagnosis. PPCMP women were younger (P<0.001), more likely to be blacks, and had less comorbidities than non-PPCMP patients. PPCMP women had better survival than non-PPCMP women (P=0.01) with a 2-year survival of 83%. Multivariable risk factor adjustment analysis showed that the improved survival was likely because of younger age and fewer comorbidities. At 36 months, a proportion of 48% PPCMP received heart transplantation. Recovery occurred at a frequency of 6% and 2% in the PPCMP and non-PPCMP groups (P=0.1). Adverse event rates were similar in PPCMP and non-PPCMP patients except for higher cardiac arrhythmias and respiratory failure in the non-PPCMP in the first 3 months post implant. Conclusions— PPCMP women who receive durable mechanical circulatory support have a better survival than women with non-PPCPM. The improved survival observed in PPCMP is likely related to their fewer comorbidities and younger age. Myocardial recovery was uncommon and less than half of women with end-stage PPCPM received heart transplantation after 3 years of mechanical support.

Outcomes following implantation of mechanical circulatory support in adults with congenital heart disease: An analysis of the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS)

BACKGROUND Adults with congenital heart disease represent an expanding and unique population of patients with heart failure (HF) in whom the use of mechanical circulatory support (MCS) has not been characterized. We sought to describe overall use, patient characteristics, and outcomes of MCS in adult congenital heart disease (ACHD). METHODS All patients entered into the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) between June 23, 2006, and December 31, 2015, were included. Patients with ACHD were identified using pre-operative data and stratified by ventricular morphology. Mortality was compared between ACHD and non-ACHD patients, and multivariate analysis was performed to identify predictors of death after device implantation. RESULTS Of 16,182 patients, 126 with ACHD stratified as follows: systemic morphologic left ventricle (n = 63), systemic morphologic right ventricle (n = 45), and single ventricle (n = 17). ACHD patients were younger (42 years ± 14 vs 56 years ± 13; p < 0.0001) and were more likely to undergo device implantation as bridge to transplant (45% vs 29%; p < 0.0001). A higher proportion of ACHD patients had biventricular assist device (BiVAD)/total artificial heart (TAH) support compared with non-ACHD patients (21% vs 7%; p < 0.0001). More ACHD patients on BiVAD/TAH support were INTERMACS profile 1 compared with patients on systemic left ventricular assist device (LVAD) support (35% vs 15%; p = 0.002). ACHD and non-ACHD patients with LVADs had similar survival; survival was worse for patients on BIVAD/TAH support. BiVAD/TAH support was the only variable independently associated with mortality (early phase hazard ratio 4.4; 95% confidence interval, 1.8-11.1; p = 0.001). For ACHD patients receiving MCS, ventricular morphology was not associated with mortality. CONCLUSIONS ACHD patients with LVADs have survival similar to non-ACHD patients. Mortality is higher for patients requiring BiVAD/TAH support, potentially owing to higher INTERMACS profile. These outcomes suggest a promising role for LVAD support in ACHD patients as part of the armamentarium of therapies for advanced HF.

Second annual Pediatric Interagency Registry for Mechanical Circulatory Support (Pedimacs) report: Pre-implant characteristics and outcomes

BACKGROUND Expanded use of pediatric ventricular assist devices (VADs) has decreased mortality in children awaiting heart transplantation. Pediatric Interagency Registry for Mechanical Circulatory Support (Pedimacs), a National Heart, Lung, and Blood Institute-sponsored North American database, provides a platform to understand this emerging population. METHODS Between September 2012 and September 2016, patients aged younger than 19 years who underwent VAD implantation were enrolled in Pedimacs. FDA approved durable devices as well as temporary support devices were included. The second annual report updates the current Pedimacs data. Patients implanted with temporary devices are included in Pedimacs and this analysis includes this group of paracorporeal continuous flow VADs. RESULTS Over the 4 years, 42 hospitals implanted 432 devices in 364 patients less than 19 yrs of age. Diagnoses included cardiomyopathy in 223 (61%), myocarditis in 41 (11%), and congenital heart disease in 77 (21%), of which 48 had single-ventricle physiology. At implant, 87% were at Intermacs patient profile 1 or 2. The age distribution of children (59% male) supported on VAD included 69 (19%) aged younger than 1 year, 66 (18%) aged 1 to 6 years, 56 (15%) aged 6 to 10 years, and 173 (48%) aged 11 to 19 years. Median follow-up was 2.2 months (range, 1 day to 41.5 months). Median (interquartile) age at implant was 1.7 (0.3-10.0) years for paracorporeal continuous-flow pumps (n = 60), 1.7 (0.4-5.3) years for paracorporeal pulsatile pumps (n = 105), and 15.0 (11.3-16.9) years for implantable continuous-flow pumps (n = 174). Support strategies included LVAD in 293 (80%), biventricular device in 55 (15%), and total artificial heart in 8 (2%). Nearly 50% of patients underwent transplantation within 6 months, with overall mortality of 19%. Adverse event burden continues to be high. CONCLUSIONS Pedimacs constitutes the largest longitudinal pediatric VAD registry. Preimplant data across centers will be helpful at creating shared protocols with which to improve outcomes. Adverse events continue to be the major challenge, especially among the young critically ill children with complex congenital disease.

High early event rates in patients with questionable eligibility for advanced heart failure therapies: Results from the Medical Arm of Mechanically Assisted Circulatory Support (Medamacs) Registry

BACKGROUND The prognosis of ambulatory patients with advanced heart failure (HF) who are not yet inotrope dependent and implications for evaluation and timing for transplant or destination therapy with a left ventricular assist device (DT-LVAD) are unknown. We hypothesized that the characteristics defining eligibility for advanced HF therapies would be a primary determinant of outcomes in these patients. METHODS Ambulatory patients with advanced HF (New York Heart Association class III-IV, Interagency Registry for Mechanically Assisted Circulatory Support profiles 4-7) were enrolled across 11 centers from May 2013 to February 2015. Patients were stratified into 3 groups: likely transplant eligible, DT-LVAD eligible, and ineligible for both transplant and DT-LVAD. Clinical characteristics were collected, and patients were prospectively followed for death, transplant, and left ventricular assist device implantation. RESULTS The study enrolled 144 patients with a mean follow-up of 10 ± 6 months. Patients in the ineligible cohort (n = 43) had worse congestion, renal function, and anemia compared with transplant (n = 51) and DT-LVAD (n = 50) eligible patients. Ineligible patients had higher mortality (23.3% vs 8.0% in DT-LVAD group and 5.9% in transplant group, p = 0.02). The differences in mortality were related to lower rates of transplantation (11.8% in transplant group vs 2.0% in DT-LVAD group and 0% in ineligible group, p = 0.02) and left ventricular assist device implantation (15.7% in transplant group vs 2.0% in DT-LVAD group and 0% in ineligible group, p < 0.01). CONCLUSIONS Ambulatory patients with advanced HF who were deemed ineligible for transplant and DT-LVAD had markers of greater HF severity and a higher rate of mortality compared with patients eligible for transplant or DT-LVAD. The high early event rate in this group emphasizes the need for timely evaluation and decision making regarding lifesaving therapies.

Characteristics of patients with pulmonary venoocclusive disease awaiting transplantation.

RATIONALE Pulmonary venoocclusive disease (PVOD) is an uncommon cause of pulmonary arterial hypertension (PAH). However, unlike PAH, treatment options for PVOD are usually quite limited. The impact of the lung allocation score on access to transplantation for patients with PVOD and the clinical course of these patients have not been well-described. OBJECTIVES To examine the association between the diagnosis of PVOD and lung transplantation for patients on the transplant waiting list. METHODS Patients with a diagnosis of PVOD and PAH registered on the United Network for Organ Sharing wait list for transplantation from May 4, 2005 to May 3, 2013 were included. Lung transplantation was the primary outcome measure. Multivariable analyses were performed to determine the odds of dying or receiving a lung transplant after listing. Survival was compared using Kaplan-Meier and competing risks methods. RESULTS Of 12,251 patients listed for lung transplantation, 49 with PVOD and 647 with PAH were identified. There were no significant differences in the lung allocation score between patients with PVOD and PAH at listing, transplant, or wait list removal for death/too sick for transplant. By 6 months, 22.6% of patients with PVOD had been removed from the wait list due to death, compared with 11.0% of patients with PAH (Chi-square P = 0.03). Patients with PVOD who died or were considered too sick for transplant were removed from the waiting list sooner after listing (22 vs. 105 d, P = 0.08). There was no difference in the proportion of patients with PVOD and PAH transplanted (50.0 vs. 47.6%, P = 0.60). CONCLUSIONS In the lung allocation score era, patients with PVOD may be at higher risk for death while on the transplant waiting list. After wait list registration, close monitoring for disease progression is advised.

Zolpidem use and motor vehicle collisions in older drivers

OBJECTIVE Prescription sleep medication use is most prevalent among women and older adults. Morning drowsiness and impaired coordination are side effects of sleep medications that may affect driving safety. The association between current use of zolpidem-containing medications and motor vehicle collisions (MVCs) was evaluated among drivers of advanced age. METHODS Participants were current drivers aged ≥70 years residing in north-central Alabama, spoke English, had a valid drivers license, and had driven within the past three months (n = 2000). Current zolpidem use was determined by pill bottle review. The participants five-year MVC history was determined from Alabama Department of Public Safety accident reports. The five-year MVC and at-fault MVC rate ratios (RR) were estimated comparing zolpidem users with nonusers in the overall sample and a priori-defined age and sex subgroups. RESULTS The unadjusted RR (95% confidence interval [CI]) of MVCs comparing zolpidem users with nonusers was attenuated after adjustment (1.46 [1.02-2.08] and 1.38 [0.97-1.98], respectively). Among women, the unadjusted and adjusted RRs (95% CI) were 1.65 (1.03-2.66) and 1.61 (1.00-2.60), respectively. The unadjusted and adjusted RRs (95% CI) among those aged 80 years or more were 2.24 (1.19-4.57) and 2.35 (1.20-4.61), respectively. There were no statistically significant associations among men or participants less than 80 years old. Similar patterns were present for at-fault MVCs. CONCLUSION Current zolpidem users, specifically women and individuals aged 80 years or more, had higher MVC rates than nonusers. Practitioners should consider behavioral treatment before initiating low doses of zolpidem and increasing it as needed to achieve restorative sleep in women and individuals aged 80 years or more to reduce the risk of zolpidem-associated MVCs.

Association of discoid lupus erythematosus with clinical manifestations and damage accrual in a multiethnic lupus cohort.

To determine the clinical manifestations and disease damage associated with discoid rash in a large multiethnic systemic lupus erythematosus (SLE) cohort.