Among all 5,213 patients, baseline creatine clearance levels were >60 mL/min in 1,203 patients (23 percent); >30 mL/min but ≤60 mL/min in 2,827 (54 percent); and ≤30 mL/min in 1,029 (20 percent). In addition, 154 patients (3 percent) were on dialysis at baseline.

After the procedure, the primary composite of all-cause mortality, stroke and new dialysis requirement occurred in 1.4 percent of patients with creatine clearance >60 mL/min; 2.7 percent of patients with creatine clearance >30 mL/min but ≤60 mL/min; 5.2 percent of patients with creatine clearance ≤30; and 7.8 percent for patients on dialysis.

Patients with lower creatine clearance had poorer 30-day and one-year outcomes. After 30 days, patients on dialysis had higher rates of all-cause mortality, while patients with creatine clearance ≤30 mL/min or on dialysis had significantly higher rates of bleeding. After one year, all-cause mortality occurred in nearly one-third of patients with creatine clearance ≤30 mL/min or on dialysis.

The study's findings demonstrate that patients with renal disease have a higher risk of adverse outcomes after TMVr, the authors write, adding their results "should be incorporated in the patient selection and shared decision-making process." They conclude future research is "warranted" to determine both the "underlying mechanism of poorer outcomes" after TMVr and the "optimal mitral valve treatment strategy" in these patients.

Shah B, Villablanca PA, Vemulapalli S, et al. Circ Cardiovasc Interv 2019;Feb 1:[Epub ahead of print].

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The primary endpoint of death due to the composite of CHD, nonfatal myocardial infarction (MI), ischemic stroke or unstable angina requiring hospitalization occurred in 901 (9.5 percent) patients in the alirocumab group and 1,052 (11.1 percent) patients in the placebo group, with four-year Kaplan-Meier estimates of 12.5 percent and 14.5 percent, respectively. The effect of alirocumab was greater after the first year.

A total of 726 (3.8 percent) patients died during the trial, with fewer deaths in the alirocumab group than the placebo group (334 [3.5 percent] vs. 392 [4.1percent], respectively).

Due to the previous findings of a delayed benefit of lipid-lowering therapies, the researchers examined death among 8,242 patients (44 percent of the study cohort) who were eligible for ≥3 years of follow-up. Among these patients, the benefit of alirocumab on all-cause death appeared more pronounced compared with the overall trial population.

Patients with nonfatal cardiovascular events were at increased risk for cardiovascular and noncardiovascular deaths. Alirocumab reduced total nonfatal cardiovascular events and thereby may have attenuated the number of noncardiovascular deaths.

A post-hoc analysis found that, compared with patients with lower LDL-C, patients with baseline LDL-C ≥100 mg/dL had a greater absolute risk of death and a larger mortality benefit from alirocumab. In the alirocumab group, all-cause death declined with achieved LDL-C at four months of treatment, to a level of approximately 30 mg/dL.

According to the researchers, findings from this study indicate that patients with ACS who are unable to adequately reduce their LDL-C on conventional lipid-lowering therapies may benefit from alirocumab treatment.

"The findings indicate the long-term treatment with alirocumab in appropriately selected patients may result in prolongation of life," the researchers conclude.

Steg PG, Szarek M, Bhatt DL, et al. Circulation 2019;May 23:[Epub ahead of print].

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Patients underwent prospective evaluations comprising assessment of cardiac parameters, functional status by six-minute walk test (6MWT), quality of life using the Kansas City Cardiomyopathy Questionnaire and survival. Centralized health records were used to determine hospital service use pre- and post-diagnosis.

A multivariable model combining age, UK National Amyloidosis Center (NAC) ATTR Disease Stage, left ventricular ejection fraction (LVEF), genotypic subgroup and 6MWT distance at diagnosis revealed each was independently associated with patient survival: age (hazard ratio [HR], 1.037 per year; NAC ATTR Disease Stage (HR, 2.049, p=0.001 for stage II; HR, 3.705, p<0.001 for stage III vs. stage I); LVEF (HR, 0.978 per 1 percent increase; p=0.003); genotypic subgroup (HR, 2.071; p<0.001 for V122I-hATTR-CM; HR, 2.727; p=0.002 for non–V122I-hATTR-CM; vs. ATTRwt-CM); and 6MWT distance (HR, 0.881 per 50-m increase; p<0.001).

There was substantial diagnostic delay, with patients using hospital services a median (interquartile range) of 17 (9-27) times during the three years before diagnosis, by which time quality of life was poor; diagnosis of ATTRwt-CM was delayed more than four years after presentation with cardiac symptoms in 4 percent of cases.

Patients with V122I-hATTR-CM were significantly more impaired functionally and had worse measures of cardiac disease (p<0.001) at the time of diagnosis, a greater decline in quality of life, and poorer survival (p<0.001), compared with the other subgroups.

"In summary, ATTR-CM is being increasingly recognized, although there remains much work to be done to establish the diagnosis earlier in the course of the disease, the natural history of which is gradual progression and death some three to 10 years from diagnosis," the authors conclude.

"In this era of promising novel therapies for ATTR amyloidosis, earlier diagnosis assumes greater importance and argues strongly for the inclusion of cardiac magnetic resonance imaging and bone scintigraphy early in the investigative pathway of patients with cardiac failure or cardiomyopathy of uncertain etiology."

Lane T, Fontana M, Martinez-Naharro A, et al. Circulation 2019;May 21:[Epub ahead of print].

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However, the 30-day stroke rate was significantly higher among patients in the bicuspid cohort than in the tricuspid cohort (2.5 vs. 1.6 percent; absolute RD, 0.89 percent; HR, 1.57).

There was no significant difference in one-year mortality between the propensity-score matched bicuspid and tricuspid groups (10.5 vs. 12.0 percent; absolute RD, 1.48 percent; HR, 0.90). No significant difference in one-year stroke rate was seen between the two groups (3.4 vs. 3.1 percent; absolute RD, 0.34 percent; HR, 1.28).

In both groups, valve function was significantly improved after TAVR and was maintained at 30 days and one year. At 30 days and one year, no significant differences in valve hemodynamics (aortic valve gradients and areas) and paravalvular aortic regurgitation was seen between the groups.

The greater calcium burden that often accompanies the bicuspid valve anatomy, which may have required more frequent balloon dilatation before and after TAVR are among factors the researchers suggest could contribute to the higher 30-day stroke rate in this group.

Procedural complexity may have led to greater cerebral embolization of debris, and cerebral embolic protection was not used in most patients in this analysis. Their routine use during TAVR in bicuspid anatomy could reduce procedure-related strokes.

This analysis shows "the contemporary outcomes of a third-generation balloon-expandable TAVR in bicuspid aortic stenosis and represents not only the evolution of device technology but also likely operator experience, improved imaging, and procedural advancements," the authors write.

They add that due to the possibility of selection bias and the absence of a control group treated surgically for bicuspid stenosis in this study, randomized trials are needed to adequately assess the efficacy and safety of TAVR for bicuspid aortic stenosis.

Makkar RR, Yoon SH, Leon MB, et al. JAMA 2019;321:2193-2202.

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